bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural Sociology
Authors: Garcia Nick , Lobao Linda
Published: August 2018

Rural sociology is a unique area of sociological inquiry. Its institutional development leaves it perhaps the most independent of all sociological subfields. Rural sociology in the United States emerged in the early 20th century when federal funding was earmarked to the land grant universities (public universities) to study and assist the farm population. Separate “rural” sociology departments appeared gradually within colleges of agriculture that paralleled the substantive areas found in general sociology departments. Thus, one finds in rural sociology a replication of many core areas in general sociology but with a rural twist—inequality, demography, work/labor markets, race/ethnicity, gender, community, and so forth. Over time, additional rural-oriented specialty areas emerged, notably the sociology of agriculture and natural resource/environmental sociology. Rural sociology has also expanded globally. As a consequence, the substantive scope of contemporary research is large and varied. What knits the work together is a focus on the geographic periphery, that is, the places, populations, and forms of social activity found in rural areas globally which has provided boundary and meaning to the field. In addition to its broad substantive scope, rural sociology is characterized by a distinct research approach. Research tends to be comparative: rural places and populations are often set in contrast with regard to their urban counterparts to ascertain similarities and differences. In this way, rural sociological research is often said to challenge the urban bias of general sociology. Disciplinary practice is also distinct. While there are few departments with rural sociology in their name today, courses and specializations in the field are found across many land grant universities. There is a long tradition of cross-disciplinary linkages particularly with agricultural economics, the environmental sciences, and more recently geography. Rural sociologists have been highly active in federal, state, and local public policy circles and in public sociology efforts that contribute to community development, sustainable agricultural and food systems, and social and environmental justice. In terms of work in the profession, rural sociologists also work outside of colleges of agriculture, within government agencies, international development agencies, and across governmental and non-governmental institutions. Although rural populations will continue to decline globally, there is reason to think that rural sociology will have broad influence in the future because the research areas it encompasses are of growing interest to social scientists, policymakers, and the public at large. Issues addressed by rural sociologists pertaining to the sustainability of the food system, climate/environmental change, and rural poverty are among the most pressing public concerns today.
Lost Generation
Authors: Monk Craig
Published: August 2018

Though first intended to denote Americans brought to Europe by the First World War, the “Lost Generation” refers to writers and other artists from the United States who took up residence in Paris in the 1920s and 1930s. The words themselves were first attributed to Gertrude Stein by Ernest Hemingway. In surveying the waste of the conflict, Stein observed the lack of surviving male role models and supposedly defined, in fact, a generation of lost young men that might transcend national origin. American expatriation is as old as the United States, of course, but Stein’s comments brought attention to Americans who came to Europe, or returned to the continent, in the post–World War I period. Writers from the United States discussed, at length, what they believed to be the provincial and restrictive attitudes of their homeland, so that the perception grew quickly that Americans abroad were in Europe to tempt debauchery. Harold Stearns, a prominent social critic, led a call for young people to venture beyond the United States, but his own experience in France was punctuated by drinking and gambling. Indeed, by the time that the idea of a Lost Generation started to gain currency, the “lost” in the moniker had truly moved from “abandoned” to a sense of moral dissipation, and reports of expatriate mischief had been reinforced by the publication in 1926 of Hemingway’s The Sun Also Rises, a fictionalized retelling of expatriate life. While a wave of Americans had spread out over the continent, a colony of artists from the United States really had established themselves in Paris, using the mechanisms of a burgeoning print culture to reject perceptions about them and to forge new collaborations with their European hosts. Successive waves of expatriates were finally blunted by the stock market crash in New York in 1929, and those Americans who had returned home began to provide serious analysis of a decade spent abroad, most commonly defending their cohort or disavowing, outright, a Lost Generation. Some expatriates who stayed abroad through the 1930s were caught up in the Second World War, and their repatriation was connected, inextricably, with those European artists who fled that conflict. By the late 1940s, a vibrant cohort of writers and other artists from the United States were again flocking to Paris. Once more, Americans abroad were rejecting the Lost Generation moniker, but this time it was to differentiate their experiences from those of their predecessors.
ANALYTICAL MODEL TO ESTIMATE EQUIVALENT DOSE FROM INTERNAL NEUTRONS IN PROTON THERAPY OF CHILDREN WITH INTRACRANIAL TUMORS
Authors: Gallagher Kyle J , Taddei Phillip J
Published: August 2018

This study developed a computationally efficient and easy-to-implement analytical model to estimate the equivalent dose from secondary neutrons originating in the bodies (‘internal neutrons’) of children receiving intracranial proton radiotherapy. A two-term double-Gaussian mathematical model was fit to previously published internal neutron equivalent dose per therapeutic absorbed dose versus distance from the field edge calculated using Monte Carlo simulations. The model was trained using three intracranial proton fields of a 9-year-old girl. The resulting model was tested against two intracranial fields of a 10-year-old boy by comparing the mean doses in organs at risk of a radiogenic cancer estimated by the model versus those previously calculated by Monte Carlo. On average, the model reproduced the internal neutron organ doses in the 10-year-old boy within 13.5% of the Monte Carlo at 3–10 cm from the field edge and within a factor of 2 of the Monte Carlo at 10–20 cm from the field edge. Beyond 20 cm, the model poorly estimated H/DRx, however, the values were very small, at <0.03 mSv Gy−1.
Changes in adiposity and other factors in relation to age at natural menopause: analyses from the coronary artery risk development (CARDIA) study
Authors: Costanian Christy , McCague Hugh , Edgell Heather , Ardern Chris I. , Tamim Hala
Published: August 2018

Objective:

The age at natural menopause has subsequent health implications. Earlier age at natural menopause is a risk factor for cardiovascular disease, atherosclerosis, and stroke. Despite extensive study, no clear and conclusive association between anthropometric measures and age at natural menopause has emerged. This study aims to assess whether baseline and/or longitudinal changes in adiposity are associated with age at natural menopause.

Methods:

In all, 2,030 premenopausal women from the Coronary Artery Risk Development in Young Adults study—a prospective study with 25 years follow-up—were included for analysis from 1985 to 1986 until menopause was attained. Anthropometry included body mass index and waist circumference. Discrete-time survival analysis was then used to determine the association between anthropometric measures at baseline, and also their changes with age at natural menopause, while adjusting for various time-varying and invariant covariates in separate models for body mass index and waist circumference.

Results:

Multivariate Cox regression analysis showed that baseline body mass index (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.94-0.98) and baseline waist circumference (HR 0.98, 95% CI 0.97-0.99) significantly increased the risk of later age at natural menopause. Neither time-varying body mass index nor waist circumference indicating change across time associated with age at natural menopause. Premenopausal hypertension was strongly associated with an earlier age at natural menopause.

Conclusion:

These findings show that age at natural menopause is partly determined by modifiable factors such as premenopausal hypertension and baseline adiposity. These results highlight the importance of both control and prevention of cardiovascular risk factors such as excess weight in early to mid-adulthood before menopause onset.
Functional Outcome Scores With Standard Myoelectric Prostheses in Below-Elbow Amputees
Authors: Salminger Stefan , Vujaklija Ivan , Sturma Agnes , Hasenoehrl Timothy , Roche Aidan D. , Mayer Johannes A. , Hruby Laura A. , Aszmann Oskar C.
Published: August 2018

Objective

The aim of the study was to report normative outcome data of prosthetic hand function in below-elbow amputees using four different objective measurements closely related to activities of daily living.

Design

Seventeen patients who underwent prosthetic fitting after unilateral below-elbow amputation were enrolled in this study. Global upper extremity function was evaluated using the Action Research Arm Test, Southampton Hand Assessment Procedure, the Clothespin-Relocation Test, and the Box and Block Test, which monitor hand and extremity function.

Results

The patients achieved a mean ± SD Action Research Arm Test score of 35.06 ± 4.42 of 57. The mean ± SD Southampton Hand Assessment Procedure score was 65.12 ± 13.95 points. The mean ± SD time for the Clothespin-Relocation Test was 22.57 ± 7.50 secs, and the mean ± SD score in the Box and Block Test was 20.90 ± 5.74.

Conclusions

In the current economic situation of health care systems, demonstrating the effectiveness and necessity of rehabilitation interventions is of major importance. This study reports outcome data of below-elbow amputees and provides a useful guide for expected prosthetic user performance.
The Influence of Local Anesthesia Depth on Procedural Pain During Fluoroscopically Guided Lumbar Transforaminal Epidural Injections
Authors: Baek In Chan , Choi Su Youn , Suh Jiwoo , Kim Shin Hyung
Published: August 2018

Objectives

The aim of the study was to evaluate the influence of the depth of local anesthesia application on procedural pain during lumbar transforaminal epidural steroid injection.

Design

Sixty-eight patients were enrolled who were scheduled for single-level, unilateral fluoroscopically guided lumbar transforaminal epidural steroid injection. Patients were randomly allocated to receive either subcutaneous local anesthesia (group S) or deep local anesthesia (group D) for transforaminal epidural steroid injection. The data related to pain and technical performance during the procedure was compared. In addition, the incidence of injection site soreness was assessed 2 wks after transforaminal epidural steroid injection.

Results

Sixty-seven patients completed all assessments (group S, n = 33; group D, n = 34). There was no significant difference in procedural pain and discomfort level between the groups (P = 0.151, P = 0.183, respectively). Patients in group D showed lower behavioral pain scores (P = 0.017). There was no significant difference in the numbers of needle manipulations, fluoroscopy time, and radiation dose during the procedure between the groups. Two patients in group S and three in group D complained of injection site soreness after transforaminal epidural steroid injection for a few days, but there was no significant difference in its incidence (P = 0.667).

Conclusions

Deep local anesthesia to reduce procedural pain during transforaminal epidural steroid injection seems to have no significant clinical benefit compared with conventional subcutaneous local anesthesia.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Reduce procedural pain by considering clinical factors of the patient during fluoroscopically guided lumbar transforaminal epidural injections.

Upon completion of this article, the reader should be able to: (1) Understand the potential impact of procedural pain on the performance of transforaminal epidural steroid injections; (2) Distinguish cutaneous nociceptive afferents from nociceptive afferents in muscle; and (3) Explain the factors to reduce procedural pain during fluoroscopically guided lumbar transforaminal epidural injections.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Muscle Strength and Aerobic Capacity in HIV-Infected Patients: A Systematic Review and Meta-Analysis
Authors: Gomes-Neto Mansueto , Rodriguez Indira , Lédo Ana P. , Vieira João P. B. , Brites Carlos
Published: August 2018

Background:

Physical impairment is highly prevalent in HIV-infected patients. We conducted a systematic review of published studies that included studies comparing muscle function in HIV-infected patients to matched healthy controls, and studies comparing aerobic capacity in HIV-infected patients with that observed in matched healthy controls.

Design:

Systematic review and meta-analysis.

Methods:

We searched for references on MEDLINE, SciELO, Cumulative Index to Nursing and Allied Health (CINAHL), and Scopus up to December 2017. Weighted mean differences and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test.

Results:

A total of 30 studies, covering 2148 healthy controls and 2161 HIV-infected patients, fulfilled the inclusion criteria. The average muscle strength and aerobic capacity were significantly lower in HIV-infected patients. Meta-analysis revealed moderate-quality evidence of weaker muscle strength and aerobic capacity in HIV-infected patients. A significant difference in lower-body strength of 1.07 (95% CI: 0.29 to 1.84) was found for participants in the healthy control group compared with HIV group. A significant difference in aerobic capacity (peak VO2) of 8.4 (95% CI: 4.8 to 12.0) was found for participants in the healthy control group compared with HIV group.

Conclusions:

Muscle strength and aerobic capacity of HIV-infected patients are reduced in comparison with healthy controls. Additional studies are needed to define the best interventions to improve the physical function in HIV-infected patients.
EBADIMEX: An empirical Bayes approach to detect joint differential expression and methylation and to classify samples
Authors: Madsen Tobias , Świtnicki Michał , Juul Malene , Pedersen Jakob Skou
Published: August 2018

1

DNA methylation and gene expression are interdependent and both implicated in cancer development and progression, with many individual biomarkers discovered. A joint analysis of the two data types can potentially lead to biological insights that are not discoverable with separate analyses. To optimally leverage the joint data for identifying perturbed genes and classifying clinical cancer samples, it is important to accurately model the interactions between the two data types.

Here, we present EBADIMEX for jointly identifying differential expression and methylation and classifying samples. The moderated t-test widely used with empirical Bayes priors in current differential expression methods is generalised to a multivariate setting by developing: (1) a moderated Welch t-test for equality of means with unequal variances; (2) a moderated F-test for equality of variances; and (3) a multivariate test for equality of means with equal variances. This leads to parametric models with prior distributions for the parameters, which allow fast evaluation and robust analysis of small data sets.

EBADIMEX is demonstrated on simulated data as well as a large breast cancer (BRCA) cohort from TCGA. We show that the use of empirical Bayes priors and moderated tests works particularly well on small data sets.
Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures
Authors: Pizzorno Andrés , Terrier Olivier , de Lamballerie Claire Nicolas , Julien Thomas , Padey Blandine , Traversier Aurélien , Roche Magali , Hamelin Marie-Eve , Rhéaume Chantal , Croze Séverine , Escuret Vanessa , Poissy Julien , Lina Bruno , Legras-Lachuer Catherine , Textoris Julien , Boivin Guy , Rosa-Calatrava Manuel
Published: August 2018

Background:

Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials.

Methods:

We exploitedin vivoglobal transcriptomic signatures of infection directly obtained from a patient cohort to determine a shortlist of already marketed drugs with newly identified, host-targeted inhibitory properties against influenza virus. The antiviral potential of selected repurposing candidates was further evaluatedin vitro, in vivoandex vivo.

Results:

Our strategy allowed the selection of a shortlist of 35 high potential candidates out of a rationalized computational screening of 1,309 FDA-approved bioactive molecules, 31 of which were validated for their significantin vitroantiviral activity. Ourin vivoandex vivoresults highlight diltiazem, a calcium channel blocker currently used in the treatment of hypertension, as a promising option for the treatment of influenza infections. Additionally, transcriptomic signature analysis further revealed the so far undescribed capacity of diltiazem to modulate the expression of specific genes related to the host antiviral response and cholesterol metabolism. Finally, combination treatment with diltiazem and virus-targeted oseltamivir neuraminidase inhibitor further increased antiviral efficacy, prompting rapid authorization for the initiation of a Phase II clinical trial.

Conclusions:

This original, host-targeted, drug repurposing strategy constitutes an effective and highly reactive process for the rapid identification of novel anti-infectious drugs, with potential major implications for the management of antimicrobial resistance and the rapid response to future epidemic or pandemic (re)emerging diseases for which we are still disarmed.
A unified model for microtubule rescue
Authors: Fees Colby P. , Moore Jeffrey K.
Published: August 2018

How microtubules transition from depolymerization to polymerization, known as rescue, is poorly understood. Here we examine two models for rescue: 1) an ‘end-driven’ model in which the depolymerizing end stochastically switches to a stable state; and 2) a ‘lattice-driven’ model in which rescue-sites are integrated into the microtubule prior to depolymerization. We test these models using a combination of computational simulations andin vitroexperiments with purified tubulin. Our findings support the ‘lattice-driven’ model by identifying repeated rescue sites in microtubules. In addition, we discover an important role for divalent cations in determining the frequency and location of rescue sites. We use ‘wash-in’ experiments to show that divalent cations inhibit rescue during depolymerization, but not during the polymerization. We propose a unified model in which rescues are driven by embedded rescue sites in microtubules, but the activity of these sites is influenced by changes in the depolymerizing ends.
The Emotional Glue of the Senses: Affective Certainty and Congruency in the Rubber Hand Illusion
Authors: Filippetti Maria Laura , Kirsch Louise P. , Crucianelli Laura , Fotopoulou Aikaterini
Published: August 2018

Our sense of body ownership relies on integrating different sensations according to their temporal and spatial congruency. Nevertheless, there is ongoing controversy about the role ofaffective congruencyduring multisensory integration, i.e. whether the stimuli to be perceived by the different sensory channels are congruent or incongruent in terms of their affective quality. In the present study, we applied a widely used multisensory integration paradigm, the Rubber Hand Illusion, to investigate the role of affective, top-down aspects of sensory congruency between visual and tactile modalities in the sense of body ownership. In Experiment 1 (N = 36), we touched participants with either soft or rough fabrics in their unseen hand, while they watched a rubber hand been touched synchronously with the same fabric or with a ‘hidden’ fabric of ‘uncertain roughness’. In Experiment 2 (N = 50), we used the same paradigm as in Experiment 1, but replaced the ‘uncertainty’ condition with an ‘incongruent’ one, in which participants saw the rubber hand being touched with a fabric of incongruent roughness and hence opposite valence. We found that certainty (Experiment 1) and congruency (Experiment 2) between the felt and vicariously perceived tactile affectivity led to higher subjective embodiment compared to uncertainty and incongruency, respectively, irrespective of any valence effect. Our results suggest that congruency in the affective top-down aspects of sensory stimulation is important to the multisensory integration process leading to embodiment, over and above temporal and spatial properties.
A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites
Authors: Tang Yong , Meister Thomas R. , Walczak Marta , Pulkoski-Gross Michael J. , Hari Sanjay B. , Sauer Robert T. , Amberg-Johnson Katherine , Yeh Ellen
Published: August 2018

Endosymbiosis has driven major molecular and cellular innovations.Plasmodiumspp. parasites that cause malaria contain an essential, non-photosynthetic plastid, the apicoplast, which originated from a secondary (eukaryote-eukaryote) endosymbiosis. To discover organellar pathways with evolutionary and biomedical significance, we performed a mutagenesis screen for essential genes required for apicoplast biogenesis inP. falciparum.Apicoplast-minusmutants were isolated using a chemical rescue that permits conditional disruption of the apicoplast and a new fluorescent reporter for organelle loss. Five candidate genes were validated (out of 12 identified), including a TIM-barrel protein that likely derived from a core metabolic enzyme but evolved a new activity. Our results demonstrate the first forward genetic screen to assign essential cellular functions to unannotatedP. falciparumgenes. A putative TIM-barrel enzyme and other newly-identified apicoplast biogenesis proteins open opportunities to discover new mechanisms of organelle biogenesis, molecular evolution underlying eukaryotic diversity, and drug targets against multiple parasitic diseases.
Aurora A inhibition limits centrosome clustering and promotes mitotic catastrophe in cells with supernumerary centrosomes
Authors: Navarro-Serer Bernat , Childers Eva P , Hermance Nicole M , Mercadante Dayna , Manning Amity L
Published: August 2018

The presence of supernumerary centrosomes is prevalent in cancer, where they promote the formation of transient multipolar mitotic spindles. Active clustering of supernumerary centrosomes enables the formation of a functional bipolar spindle that is competent to complete a bipolar division. Disruption of spindle pole clustering in cancer cells promotes multipolar division and generation of non-proliferative daughter cells with compromised viability. Hence molecular pathways required for spindle pole clustering in cells with supernumerary centrosomes, but dispensable in normal cells, are promising therapeutic targets. Here we demonstrate that Aurora A kinase activity is required for spindle pole clustering in cells with extra centrosomes. While cells with two centrosomes are ultimately able to build a bipolar spindle and proceed through a normal cell division in the presence of Aurora A inhibition, cells with supernumerary centrosomes form multipolar and disorganized spindles that are not competent for chromosome segregation. Instead, following a prolonged mitosis, these cells experience catastrophic divisions that result in grossly aneuploid, and non-proliferative daughter cells. Aurora A inhibition in a panel of Acute Myeloid Leukemia cancer cells has a similarly disparate impact on cells with supernumerary centrosomes, suggesting that centrosome number and spindle polarity may serve as predictive biomarkers for response to therapeutic approaches that target Aurora A kinase function.
Cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and antagonist for amylin fibrillation
Authors: Sahoo Bikash R. , Genjo Takuya , Stoddard Andrea K. , Yasuhara Kazuma , Fierke Carol A. , Ramamoorthy Ayyalusamy
Published: August 2018

In human, amyloid-beta (Aβ) and islet amyloid polypeptide (hIAPP) aggregations are linked to Alzheimer’s disease and Type-2 Diabetes, respectively. There is significant interest in better understanding the aggregation process by using chemical tools. Here, we show the ability of a cationic polymethacrylate-copolymer (PMAQA) to quickly induce β-hairpin structure and promote fibrillation in Aβ40, and to constrain the conformational plasticity of hIAPP for several days and inhibit its aggregation at sub-micromolar concentrations. NMR experiments and atomistic molecular dynamics simulations reveal that PMAQA electrostatically interacts with Aβ40’s Glu22 and Asp23 followed by β-sheet induction while it binds strongly to the closest proximity of amyloid core domain (NFGAIL) of hIAPP and restrain its structural rearrangement. This study provides a valuable approach to develop polymer-based anti-amyloid inhibitors that may diminish the population of intermediates of Aβ40 or hIAPP.
Parasite-mediated anorexia increases or decreases virulence evolution, depending on dietary context
Authors: Hite J. L. , Cressler C. E.
Published: August 2018

Parasite-mediated anorexia is a ubiquitous, but poorly understood component of host-parasite interactions. These temporary but substantial reductions in food intake (range: 4-100%) limit exposure to parasites and alter within-host physiological processes that regulate parasite development, production, and survival, such as energy allocation, immune function, host-microbiota interactions, and gastrointestinal conditions. By altering the duration, severity, and spread of infection, anorexia could substantially alter ecological, evolutionary, and epidemiological dynamics. However, these higher-order implications are typically overlooked and remain poorly understood — even though medical (e.g., non-steroidal anti-inflammatory drugs, vaccines, targeted signaling pathways, calorie restriction) and husbandry practices (e.g., antibiotic and diet use for rapid growth, nutrient supplementation) often directly or indirectly alter host appetite and nutrient intake. Here, we develop theory that helps elucidate why reduced food intake (anorexia) can enhance or diminish disease severity and illustrates that the population-level outcomes often contrast with the individual-level outcomes: treatments that increase the intake of high quality nutrients (suppressing anorexia), can drive rapid individual-level recovery, but inadvertently increase infection prevalence and select for more virulent parasites. Such a theory-guided approach offers a tool to improve targeting host nutrition to manage disease in both human and livestock populations by revealing a means to predict how nutrient-driven feedbacks will affect both the host and parasite.
SABER enables highly multiplexed and amplified detection of DNA and RNA in cells and tissues
Authors: Kishi Jocelyn Y. , Beliveau Brian J. , Lapan Sylvain W. , West Emma R. , Zhu Allen , Sasaki Hiroshi M. , Saka Sinem K. , Wang Yu , Cepko Constance L. , Yin Peng
Published: August 2018

Fluorescentin situhybridization (FISH) reveals the abun-dance and positioning of nucleic acid sequences in fixed sam-ples and can be combined with cell segmentation to produce a powerful single cell gene expression assay. However, it re-mains difficult to label more than a few targets and to visu-alize nucleic acids in environments such as thick tissue sam-ples using conventional FISH technologies. Recently, meth-ods have been developed for multiplexed amplification of FISH signals, yet it remains challenging to achieve high lev-els of simultaneous multiplexing combined with high sam-pling efficiency and simple workflows. Here, we introduce signal amplification by exchange reaction (SABER), which endows oligo-based FISH probes with long, single-stranded DNA concatemers that serve as targets for sensitive fluores-cent detection. We establish that SABER effectively ampli-fies the signal of probes targeting nucleic acids in fixed cells and tissues, can be deployed against at least 17 targets si-multaneously, and detects mRNAs with high efficiency. As a demonstration of the utility of SABER in assays involv-ing genetic manipulations, we apply multiplexed FISH of reporters and cell type markers to the identification of en-hancers with cell type-specific activity in the mouse retina. SABER represents a simple and versatile molecular toolkit to allow rapid and cost effective multiplexed imaging.
Enabling tools forToxoplasmaglycobiology
Authors: Gas-Pascual Elisabet , Ichikawa H. Travis , Sheikh M. Osman , Serji M. Isabella , Deng Bowen , Mandalasi Msano , Bandini Giulia , Samuelson John , Wells Lance , West Christopher M.
Published: August 2018

Infection by the protozoan parasiteToxoplasma gondiiis a major health risk owing to its chronic nature, ability to reactivate to cause blindness and encephalitis, and high prevalence in human populations. Like nearly all eukaryotes,Toxoplasmaglycosylates many of its proteins and lipids and assembles polysaccharides. Unlike most eukaryotes,Toxoplasmadivides and differentiates in vacuoles within host cells. While their glycans resemble canonical models, they exhibit species-specific variations that have inhibited deeper investigations into their roles in parasite biology and virulence. The genome ofToxoplasmaencodes a suite of likely glycogenes expected to assemble a range ofN-glycans,O-glycans, aC-glycan, GPI-anchors, and polysaccharides, along with their requisite precursors and membrane transporters. To facilitate genetic approaches to investigate the roles of specific glycans, we mapped probable connections between 59 glycogenes, their enzyme products, and the glycans to which they contribute. We adapted a double-CRISPR/Cas9 strategy and a mass spectrometry-based glycomics workflow to test these relationships, and conducted infection studies in fibroblast monolayers to probe cellular functions. Through the validated disruption of 17 glycogenes, we also discovered novel Glc0-2-Man6-GlcNAc2-type N-glycans, GalNAc2- and Glc-Fuc-type O-glycans, and a nuclear O-Fuc type glycan. We describe the guide sequences, disruption constructs, and mutant strains, which are freely available to practitioners for application in the context of the relational map to investigate the roles of glycans in their favorite biological processes.
CTP synthase regulation by miR-975 controls cell proliferation and differentiation inDrosophila melanogaster
Authors: Kan Woo Wai , Dzaki Najat , Azzam Ghows
Published: August 2018

CTP synthase (CTPsyn) is an essential metabolic enzyme. As a key regulator of the nucleotide pool, the protein has been found to be elevated in cancer models. In many organisms, CTPsyn compartmentalizes into filaments termed cytoophidia. ForD. melanogaster, it is only its Isoform C i.e. CTPsynIsoC which forms the structure. The fruit fly’s testis is home to somatic and germline stem cells. Both micro and macro-cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located and development is at its most rapid. Here, we report thatCTPsynIsoCoverexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately one-third of like-genotyped males. Immunostaining shows that the cause of this tumour-like phenotype is most likely due to increased numbers of both germline cells and spermatocytes. We also report that under conditions wherebymiR-975is overexpressed, greater incidences of the same bulged-phenotype coincides with induced upregulation ofCTPsynIsoC.However, RT-qPCR assays reveal that either overexpression genotype provokes a differential response in expression of a number of genes concurrently associated with CTPsyn and cancer, showing that the pathwaysCTPsynIsoCaffect andmiR-975regulate may be completely independent of each other. This study presents the first instance of consequences of miRNA-asserted regulation uponCTPsyninD. melanogaster, and further reaffirms the enzyme’s close ties to cancer and carcinogenesis.
Finally, Bulk Typing of Bacterial Species down to Strain Level using ON-rep-seq
Authors: Krych Łukasz , Castro-Mejía Josué L. , Moesby Daniel N. , Mikkelsen Morten B. , Rasmussen Morten A. , Sykulski Maciej , Nielsen Dennis S.
Published: August 2018

Despite the massive developments within culture-independent methods for detection and quantification of microorganisms during the last decade, culture-based methods remain a cornerstone in microbiology. We have developed a new method for bacterial DNA enrichment and tagmentation allowing fast (< 24h) and cost-effective species level identification and strain level differentiation using the MinION portable sequencing platform (ON-rep-seq). DNA library preparation takes less than 5h and ensures highly reproducible distribution of reads that can be used to generate strain level specific read length counts profiles (LCp). We have developed a pipeline that by correcting the random error of reads within peaks of LCp generates a set (∼10 contigs per sample; 300bp - 3Kb) of high quality (>99%) consensus reads. Whereas, the information from high quality reads is used to retrieve species level taxonomy, comparison of LCp allows for strain level differentiation. With benchmarked 288 isolates identified on a single flow cell and a theoretical throughput to evaluate over 1000 isolates, our method allows for detailed bacterial identification for less than 2$ per sample at very high speed.
Chemotactic behaviour ofEscherichia coliat high cell density
Authors: Colin Remy , Drescher Knut , Sourjik Victor
Published: August 2018

At high cell density, swimming bacteria exhibit collective motility patterns, self-organized through physical interactions of a however still debated nature. Although high-density behaviours are frequent in natural situations, it remained unknown how collective motion affects chemotaxis, the main physiological function of motility, which enables bacteria to follow environmental gradients in their habitats. Here, we systematically investigate this question in the model organismEscherichia coli, varying cell density, cell length, and suspension confinement. The characteristics of the collective motion indicate that hydrodynamic interactions between swimmers made the primary contribution to its emergence. We observe that the chemotactic drift is moderately enhanced at intermediate cell densities, peaks, and is then strongly suppressed at higher densities. Numerical simulations reveal that this suppression occurs because the collective motion disturbs the choreography necessary for chemotactic sensing. We suggest that this physical hindrance imposes a fundamental constraint on high-density behaviours of motile bacteria, including swarming and the formation of multicellular aggregates and biofilms.
Sensitive period for cognitive repurposing of human visual cortex
Authors: Kanjlia Shipra , Pant Rashi , Bedny Marina
Published: August 2018

Studies of sensory loss are a model for understanding the functional flexibility of human cortex. In congenital blindness, subsets of visual cortex are recruited during higher-cognitive tasks, such as language and math tasks. Is such dramatic functional repurposing possible throughout the lifespan or restricted to sensitive periods in development? We compared visual cortex function in individuals who lost their vision as adults (after age 17) to congenitally blind and sighted blindfolded adults. Participants took part in resting-state and task-based fMRI scans during which they solved math equations of varying difficulty and judged the meanings of sentences. Blindness at any age caused “visual” cortices to synchronize with specific fronto-parietal networks at rest. However, in task-based data, visual cortices showed regional specialization for math and language and load-dependent activity only in congenital blindness. Thus, despite the presence of long-range functional connectivity, cognitive repurposing of human cortex is limited by sensitive periods.
Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling
Authors: Stratman Amber N. , Farrelly Olivia M. , Mikelis Constantinos M. , Miller Mayumi F. , Wang Zhiyong , Pham Van N. , Davis Andrew E. , Burns Margaret C. , Pezoa Sofia A. , Castranova Daniel , Yano Joseph J. , Kilts Tina M. , Davis George E. , Gutkind J. Silvio , Weinstein Brant M.
Published: August 2018

Anti-angiogenic therapies have generated significant interest for their potential to combat tumor growth (1-6). However, the ability of tumors to overproduce pro-angiogenic ligands and overcome targeted inhibitory therapies has hampered this approach (7, 8). A novel way to circumvent this problem might be to target the resynthesis of critical substrates consumed during intracellular transduction of pro-angiogenic signals in endothelial cells, thus harnessing the tumor’s own production of excess stimulatory ligands to deplete adjacent host endothelial cells of the capacity to respond to these signals (9-12). Here we show using zebrafish and human endothelial cellsin vitrothat endothelial cells deficient inCDP-diacylglycerol synthase 2are uniquely sensitive to increased VEGF stimulation due to a reduced capacity to re-synthesize phosphoinositides, including phosphatidylinositol 4,5-bisphosphate (PIP2) a key substrate for VEGF signal transduction, resulting in VEGF-exacerbated defects in angiogenesis and angiogenic signaling (9-22). Using murine tumor allograft models (23) we show that either systemic or endothelial cell specific suppression of phosphoinositide recycling results in reduced tumor growth and reduced tumor angiogenesis. Our results suggest that inhibition of phosphoinositide recycling may provide a useful anti-angiogenic approach, and highlights the general potential of targeting the resynthesis of rate limiting signaling substrates as a valuable therapeutic strategy.

SUMMARY STATEMENT

Targeting phosphoinositide recycling during tumor angiogenesis provides a potentially uniquely effective anti-cancer therapy.
Epidemiology of Cancers in Zambia: A Significant Variation in Cancer Incidence and Prevalence across the Nation
Authors: Kalubula Maybin , Shen Heqing , Makasa Mpundu , Liu Longjian
Published: August 2018

Background

Cancers are one of the leading causes of death worldwide. More than two thirds of deaths due to cancers occur in low- and middle-income countries whereZambia belongs. This study therefore sought to assess the epidemiology of cancers in Zambia.

Methods

We conducted a retrospective observational study nested on Zambia National Cancer Registry (ZNCR) histopathological and clinical data from 2007 to 2014. Zambia Central Statistics Office (CSO)demographic datawere used to calculate prevalence and incidence rates of cancers. Age-adjusted rates and case fatality rates were estimated using standard methods. We used a Poisson Approximation for calculating 95% confidence intervals (CI).

Results

The top seven most cancer prevalent districts in Zambia have been Luangwa, Kabwe, Lusaka, Monze, Mongu, Katete and Chipata. Cervical cancer, prostate cancer, breast cancer and Kaposi’s sarcoma were the top four most prevalent cancers as well as major causes of cancer related deaths in Zambia. Standardised Incidence Rates and 95% CI for the top four cancers were: cervix uteri (186.3; CI = 181.77 – 190.83), prostate (60.03; CI = 57.03 – 63.03), breast (38.08; CI = 36.0 – 40.16) and Kaposi’s sarcoma (26.18; CI = 25.14 – 27.22).CFR were: Leukaemia (38.1%); pancreatic cancer (36.3%); lung cancer (33.3%); and brain, nervous system (30.2%). Cancers were associated with HIV withp-value of 0.000 and Pearson correlation coefficient of 0.818.

Conclusions

The widespread distribution of cancers with high prevalence in the southern zone has been perpetrated by lifestyle and sexual culture as well as geography. Intensifying cancer screening and early detection countrywide as well as changing the lifestyle and sexual culture would greatly help in the reduction of cancer cases in Zambia.
Montastraea cavernosacorallite structure demonstrates distinct morphotypes across shallow and mesophotic depth zones in the Gulf of Mexico
Authors: Studivan Michael S. , Milstein Gillian , Voss Joshua D.
Published: August 2018

This study assessed morphological variation of the depth-generalist coralMontastraea cavernosaacross shallow and mesophotic coral ecosystems in the Gulf of Mexico (GOM) using thirteen corallite metrics. While corallite structure differed significantly across sites, we observed that mean corallite diameters were smaller and spacing was greater in mesophotic corals as compared to shallow corals. Additional corallite variation, including greater mean corallite height of mesophotic samples, are hypothesized to be photoadaptive responses to low light environments. Multivariate analyses also revealed two distinct morphotypes identified by significant variation in corallite spacing with >90% accuracy. A ‘shallow’ morphotype was characterized by larger, more closely-spaced corallites, while a ‘depth-generalist’ type exhibited smaller, further-spaced corallites. Variable presence of morphotypes within some sites suggests genotypic influence on corallite morphology as there was a slight, but significant, impact of morphotype on genetic structure within shallow zones in the Flower Garden Banks. Patterns of increased algal symbiont (Symbiodiniaceae) density and chlorophyll concentration were retained in the depth-generalist morphotype even in shallow zones, identifying multiple photoadaptive strategies between morphotypes. The results of this study suggest that morphological variation amongM. cavernosarepresents a combination of genotypic variation and phenotypic plasticity rather than responses to environmental stimuli alone.
Psidium guajava in the Galapagos Islands: population genetics and history of an invasive species
Authors: Urquía Diego , Gutiérrez Bernardo , Pozo Gabriela , Pozo María José , Espín Analía , de Lourdes Torres María
Published: August 2018

The threat of invasive plant species in island populations prompts the need to better understand their population genetics and dynamics. In the Galapagos islands, this is exemplified by the introduced guava (Psidium guajava), considered one of the greatest threats to the local biodiversity due to its effective spread in the archipelago and its ability to outcompete endemic species. To better understand its history and genetics, we analyzed individuals from three inhabited islands in the Galapagos archipelago with 11 SSR markers. Our results reveal similar genetic diversity between islands, suggestive of gene flow between them. Populations appear to be distinct between the islands of San Cristobal and Isabela, with the population of Santa Cruz being composed as a mixture from both. Additional evidence for genetic bottlenecks and the inference of introduction events suggests an original introduction of the species in San Cristobal, from where it was later introduced to Isabela, and finally into Santa Cruz. Alternatively, an independent introduction event for Isabela is also possible. These results are contrasted with the historical record, providing a first overview of the history of P. guajava in the Galapagos islands and its current population dynamics.
Implantable electrical stimulation bioreactor with liquid crystal polymer based electrodes for enhanced bone regeneration at mandibular large defects in rabbit
Authors: Kim Chaebin , Yang Hoon Joo , Cho Tae Hyung , Lee Beom Seok , Gwon Tae Mok , Shin Soowon , Kim In Sook , Kim Sung June , Hwang Soon Jung
Published: August 2018

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Our previous studies demonstrated that electrical stimulation (ES) with biphasic current pulse showed proliferative effects on bone cells and enhanced secretion of bone-forming growth factors. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which has excellent bone-binding property. The bioreactor was implanted into a critical sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via bioreactor was compared with a sham control group and positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20 μg). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 171% (p< 0.001) and 210% (p < 0.001), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within bone defects and adjacent to LCP in all groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation.