bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposons
Authors: Hatanaka Yuki , Inoue Kimiko , Oikawa Mami , Kamimura Satoshi , Ogonuki Narumi , Kodama Eiichi N. , Ohkawa Yasuyuki , Tsukada Yu-ichi , Ogura Atsuo
Published: November 2015

Significance

Retrotransposons constitute substantial proportions of mammalian genomes and can be harmful when activated ectopically. DNA methylation is the major mechanism for retrotransposon silencing, but we do not know how late preimplantation embryos, which are exceptionally hypomethylated, are protected from retrotransposons. Knockdown of the histone chaperone chromatin assembly factor 1 (CAF-1) resulted in significant up-regulation of retrotransposons (e.g., long interspersed element 1) and mouse embryonic death at morula stage. CAF-1 was responsible for deposition of histone variant H3.1/3.2 and repressive histone marks, including trimethylation of histone H4 on lysine 20 (H4K20me3) and H3K9me3, at retrotransposon regions. Depletion of H4K20me3 or H3K9me3 by knockdown of specific histone methyltransferases resulted in up-regulation of retrotransposons in morulae. Thus, hypomethylated preimplantation mouse embryos are protected by repressive histone modifications mediated by CAF-1.
Recruitment of Young Bull Trout into the Metolius River and Lake Billy Chinook, Oregon
Authors: Ratliff Don , Spateholts Robert , Hill Megan , Schulz Eric
Published: November 2015

The abundance of Bull Trout Salvelinus confluentus in the Metolius River and Lake Billy Chinook, a hydroelectric reservoir, increased dramatically from 1998 to 2004, following implementation of restrictive fishery regulations. However, both adult Bull Trout and kokanee Oncorhynchus nerka (prey) populations have declined in more recent years. We investigated the relationships between Bull Trout spawner densities, emerging fry densities, and numbers of juveniles migrating into the reservoir to determine the potential role of juvenile production in this decline. We hypothesized that age-1 and older juvenile production is now limited by natal habitat capacity and that excess fry production is lost to density-dependent mortality. Bull trout redd densities in surveyed spawning reaches ranged from 14 to 39 redds/km during recent years. The estimated abundance of emerging Bull Trout fry in monitored spawning reaches has varied from about 1.0–2.5 million annually since 2005, while mean estimated densities of newly emerged fry varied from over 35/m2 in Roaring Creek during 2005 to less than 1/m2 in Jefferson Creek during 2009. Fry capture numbers from high versus low escapement broods at the Metolius River downstream trap varied by a factor of four, but capture of age-1 and age-2 juveniles did not differ substantially. These findings indicate natal Bull Trout habitats are seeded at spawner densities of 14 redds/km and higher. Fry in excess of natal habitat capacity are probably lost to density-dependent mortality factors. We estimate natural recruitment of age-1 and older Bull Trout into Lake Billy Chinook of at least 9 individuals/ha annually since 2001. Recent population bottlenecks limiting adult Bull Trout abundance occurred after juvenile recruits entered the lake and are probably related to prey availability.

Received February 23, 2015; accepted July 8, 2015
Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs
Authors: Morishita Satoru , Kawaguchi Hiroaki , Ono Tomoji , Miura Naoki , Murakoshi Michiaki , Sugiyama Keikichi , Kato Hisanori , Tanimoto Akihide , Nishino Hoyoku
Published: November 2015

Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism.
Development of suitable hydroponics system for phytoremediation of arsenic-contaminated water using an arsenic hyperaccumulator plant Pteris vittata
Authors: Huang Yi , Miyauchi Keisuke , Inoue Chihiro , Endo Ginro
Published: November 2015

In this study, we found that high-performance hydroponics of arsenic hyperaccumulator fern Pteris vittata is possible without any mechanical aeration system, if rhizomes of the ferns are kept over the water surface level. It was also found that very low-nutrition condition is better for root elongation of P. vittata that is an important factor of the arsenic removal from contaminated water. By the non-aeration and low-nutrition hydroponics for four months, roots of P. vittata were elongated more than 500 mm. The results of arsenate phytofiltration experiments showed that arsenic concentrations in water declined from the initial concentrations (50 μg/L, 500 μg/L, and 1000 μg/L) to lower than the detection limit (0.1 μg/L) and about 80% of arsenic removed was accumulated in the fern fronds. The improved hydroponics method for P. vittata developed in this study enables low-cost phytoremediation of arsenic-contaminated water and high-affinity removal of arsenic from water.
Probabilistic models of genetic variation in structured populations applied to global human studies
Authors: Hao Wei , Song Minsun , Storey John D.
Published: November 2015

Motivation: Modern population genetics studies typically involve genome-wide genotyping of individuals from a diverse network of ancestries. An important problem is how to formulate and estimate probabilistic models of observed genotypes that account for complex population structure. The most prominent work on this problem has focused on estimating a model of admixture proportions of ancestral populations for each individual. Here, we instead focus on modeling variation of the genotypes without requiring a higher-level admixture interpretation.

Results: We formulate two general probabilistic models, and we propose computationally efficient algorithms to estimate them. First, we show how principal component analysis can be utilized to estimate a general model that includes the well-known Pritchard–Stephens–Donnelly admixture model as a special case. Noting some drawbacks of this approach, we introduce a new ‘logistic factor analysis’ framework that seeks to directly model the logit transformation of probabilities underlying observed genotypes in terms of latent variables that capture population structure. We demonstrate these advances on data from the Human Genome Diversity Panel and 1000 Genomes Project, where we are able to identify SNPs that are highly differentiated with respect to structure while making minimal modeling assumptions.

Availability and Implementation: A Bioconductor R package called lfa is available at http://www.bioconductor.org/packages/release/bioc/html/lfa.html.

Contact:  jstorey@princeton.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Evaluation of hierarchical models for integrative genomic analyses
Authors: Denis Marie , Tadesse Mahlet G.
Published: November 2015

Motivation: Advances in high-throughput technologies have led to the acquisition of various types of -omic data on the same biological samples. Each data type gives independent and complementary information that can explain the biological mechanisms of interest. While several studies performing independent analyses of each dataset have led to significant results, a better understanding of complex biological mechanisms requires an integrative analysis of different sources of data.

Results: Flexible modeling approaches, based on penalized likelihood methods and expectation-maximization (EM) algorithms, are studied and tested under various biological relationship scenarios between the different molecular features and their effects on a clinical outcome. The models are applied to genomic datasets from two cancer types in the Cancer Genome Atlas project: glioblastoma multiforme and ovarian serous cystadenocarcinoma. The integrative models lead to improved model fit and predictive performance. They also provide a better understanding of the biological mechanisms underlying patients’ survival.

Availability and implementation: Source code implementing the integrative models is freely available at https://github.com/mgt000/IntegrativeAnalysis along with example datasets and sample R script applying the models to these data. The TCGA datasets used for analysis are publicly available at https://tcga-data.nci.nih.gov/tcga/tcgaDownload.jsp.

Contact:  marie.denis@cirad.fr or mgt26@georgetown.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Chemical evolution of the HC3N and N2H+ molecules in dense cores of the Vela C giant molecular cloud complex
Authors: Ohashi Satoshi , Tatematsu Ken'ichi , Fujii Kosuke , Sanhueza Patricio , Nguyen Luong Quang , Choi Minho , Hirota Tomoya , Mizuno Norikazu
Published: November 2015

We have observed the HC3N(J = 10–9) and N2H+ (J = 1–0) lines toward the Vela C molecular clouds with the Mopra 22 m telescope to study the chemical characteristics of dense cores. The intensity distributions of these molecules are similar to each other at an angular resolution of 53″, corresponding to 0.19 pc, suggesting that these molecules trace the same dense cores. We identified 25 local peaks in the velocity-integrated intensity maps of the HC3N and/or N2H+ emission. Assuming local thermodynamic equilibrium conditions, we calculated the column densities of these molecules and found a tendency for the N2H+/HC3N abundance ratio to be low in starless regions while it seems to be high in star-forming regions, similar to the tendencies in the NH3/CCS, NH3/HC3N, and N2H+/CCS abundance ratios found in previous studies of dark clouds and the Orion A giant molecular cloud (GMC). We suggest that carbon chain molecules, including HC3N, may trace chemically young molecular gas, and that N-bearing molecules, such as N2H+, may trace later stages of chemical evolution in the Vela C molecular clouds. It may be possible that the N2H+/HC3N abundance ratio of ∼1.4 divides the star-forming and starless peaks in Vela C, although it is not as clear as those in NH3/CCS, NH3/HC3N, and N2H+/CCS for the Orion A GMC. This less clear separation may be caused by our lower spatial resolution or the misclassification of star-forming and starless peaks due to the larger distance of Vela C. It might also be possible that the HC3N (J = 10–9) transition is not a good chemical evolution tracer compared with CCS (J = 4–3 and 7–6) transitions.
Muscle Triggers as a Possible Source of Pain in a Subgroup of Tension-type Headache Patients?
Authors: Arendt-Nielsen Lars , Castaldo Matteo , Mechelli Filippo , Fernández-de-las-Peñas César
Published: November 2015

Objectives:

Tension-type headache (TTH) is a common condition but the underlying etiology is not understood. Episodic TTH may develop into chronic TTH, and some possible triggers may be involved in generation and maintenance. Nociceptive generators and hyperexcitable spots in neck and shoulder regions may to some degree contribute to TTH. The current paper highlights some of the possible triggers and associated pain mechanisms involved in TTH and discusses whether inhibition of these possible triggers may provide new treatment options.

Results:

This paper presents possible pathophysiological factors in TTH, the role of muscle pain, and how referred pain from triggers can contribute to development, maintenance of sensitization, or both. Referred pain patterns from trigger points and associated muscle hyperalgesia seem to be clinically important factors. Damping the nociceptive peripheral drive may not only reduce the number of TTH attacks but may also prevent, delay the transition from episodic into more chronic TTH, or both. The role of muscle triggers in driving TTH is debated as the pathogenesis of such triggers is not fully understood. Furthermore, inhibiting the drive from the triggers does not consistently modulate TTH.

Discussion:

Understanding the possible triggers in TTH, muscle hyperalgesia, and widespread pain sensitization, may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions. Currently, there is a striking difference between the clinical observational studies favoring the role of muscle triggers in TTH and the intervention studies generally not supporting the role of muscle triggers in TTH.
Involvement of CCL3/CCR5 Signaling in Dorsal Root Ganglion in Remifentanil-induced Hyperalgesia in Rats
Authors: Li Nan , Zhang Linlin , Shu Ruichen , Ding Ling , Wang Zhifen , Wang Haiyun , Yu Yonghao , Wang Guolin
Published: November 2015

Background:

Several mechanisms of remifentanil-induced hyperalgesia in spinal cord mainly have been explained such as N-methyl-d-aspartate receptors activation, but the mechanism in dorsal root ganglion (DRG) is poorly understood. It has been reported that CCL3 may be a regulator in both inflammatory pain and hyperalgesia. In this paper we explored whether CCL3 and CCR5, the mainly receptor of CCL3, play a role in the remifentanil-induced hyperalgesia in DRG by using a rat model with remifentanil administration.

Materials and Methods:

The von Frey test and hot plate test were performed to measure the different threshold to evaluate mechanical and thermal hyperalgesia. Real-time polymerase chain reaction and Western blot analysis were used to evaluate time course of CCL3 and CCR5 expression in DRG after remifentanil infusion. The changes of glial cells and the expression of CCL3 and CCR5 were detected by immunofluorescence assay. Finally, intrathecal injection of CCL3-neutralizing antibody and maraviroc, the CCR5 antagonists, were used sevoflurane to confirm the role of CCL3/CCR5 signaling in the rat model of remifentanil-induced hyperalgesia.

Results:

Remifentanil infusion profoundly increased thermal and mechanical hyperalgesia from 2 to 48 hours according to paw withdrawal latency (PWL) and paw withdrawal thresholds (PWT) (mean±SD, hyperalgesia vs. control, 17.4±0.91 vs. 8.5±1.46 s; 20.1±0.32 vs. 9.6±0.5 g, n=8). Moreover, the expression of mRNAs and proteins of CCL3 and its receptor CCR5 in DRG were dramatically increased after remifentanil infusion as compared with the normal saline group. We also found that CCL3 and CCR5 were colocalized with glial cells or neurons. Furthermore, intrathecal injection of CCL3-neutralizing antibody (mean±SD, hyperalgesia vs. control, 17.4±0.91 vs. 8.5±1.46 s; 20.1±0.32 vs. 9.6±0.5 g, n=5) and maraviroc(mean±SD, hyperalgesia vs. control, 17.4±0.91 vs. 8.5±1.46 s; 20.1±0.32 vs. 9.6±0.5 g, n=5) were able to suppress remifentanil-related thermal and mechanical hyperalgesia according to behavioral test.

Conclusions:

The results highlighted the fact that CCL3 and its receptor CCR5 in DRG might contribute to remifentanil-induced hyperalgesia. Thus CCL3/CCR5 signaling may be further considered in the development of new therapeutic strategies.
Body Awareness as an Important Target in Multidisciplinary Chronic Pain Treatment
Authors: van der Maas Lia C.C. , Köke Albère , Bosscher Ruud J. , Twisk Jos W.R. , Janssen Thomas W.J. , Peters Madelon
Published: November 2015

Background:

The results of a recently performed randomized clinical trial showed that the effect of a multidisciplinary treatment of chronic pain patients on body awareness (BA), catastrophizing, and depression was improved by adding psychomotor therapy (PMT), an intervention targeting BA. No significant effects were found on quality of life and disability. The present follow-up study aimed to explore the relationship between improvements in BA and multidisciplinary chronic pain rehabilitation treatment outcome across treatment conditions and the possible mediating effect of BA between treatment conditions. Furthermore, the hypothesis that patients with low BA benefit more from PMT was investigated.

Methods:

In total, 94 patients with chronic pain participated in a randomized clinical trial comparing multidisciplinary treatment as usual (TAU) with TAU plus PMT. Outcome variables were health-related quality of life, disability, and depression. Self-efficacy and catastrophizing were the process variables of treatment and the potential mediating factors in the relationship between BA and the outcome variables. The data were analyzed by linear mixed-model analysis.

Results:

Improvements in BA were related to improvements in all outcome variables across treatment conditions. The relationships were partly mediated by self-efficacy, catastrophizing, or both. In the regression model with depression as the outcome variable, the regression coefficient of treatment (ie, PMT vs. TAU) decreased by 34% and became nonsignificant when BA was added as a potential mediator. Patients with low BA seemed to benefit more from PMT than patients with high BA, especially on depression, BA, and catastrophizing.

Conclusions:

BA might be an important target of treatment to improve the multidisciplinary treatment outcome in chronic pain patients. Furthermore, PMT is an intervention that seems to provide its benefits through improving BA and may be especially beneficial for patients with low BA.
Use of Looped Monofilament Instead of Braided Suture in Orthopedic Fascial Closure
Authors: Li Lily , Tai Stephen , Deo Hersh
Published: November 2015

The established method of closing fascia lata is with braided continuous sutures (eg, No. 1-Vicryl). The distal extent of the fascial incision often undermines the skin incision, hindering placement of the fascial anchoring knot. An assistant may be required for forceful retraction. Looped monofilament (eg, No. 1-PDS), with a blunt needle, allows easier fascial closure. One bite is taken through both sides of the fascia before passing the needle through the preformed loop, thus completing the anchoring stitch. No assistant is needed. Monofilament is cheap, readily available, may reduce infection and tissue reaction, and maintains tensile strength for longer than braided sutures.
Effect of Axial Length on Macular Ganglion Cell Complex Thickness and on Early Glaucoma Diagnosis by Spectral-Domain Optical Coherence Tomography
Authors: Nakanishi Hideo , Akagi Tadamichi , Hangai Masanori , Kimura Yugo , Suda Kenji , Hasegawa Tomoko , Yamada Hiroshi , Yoshikawa Munemitsu , Morooka Satoshi , Ikeda Hanako Ohashi , Yoshimura Nagahisa
Published: November 2015

Purpose:

To investigate the effects of the axial length (AL)-related ocular magnification on the thickness of the macular ganglion cell complex (mGCC), and the diagnostic accuracy of the built-in normative database of the spectral-domain optical coherence tomographic (SD-OCT) instrument for early glaucoma detection.

Methods:

This retrospective study included 41 eyes with early primary open-angle glaucoma and 36 normal eyes. The mGCC thickness within a 20-degree circle, equivalent to a 6 mm diameter in the Gullstrand model eye, was measured in the SD-OCT images. The magnification effect was corrected using Bennett formula, and the mGCC thickness within the actual 6 mm diameter circle was determined.

Results:

In normal eyes, the inferior corrected mGCC was significantly correlated with the AL (β=−0.40, P=0.028), but correction for the magnification reduced the correlation. In 38 nonhighly myopic eyes, the sensitivity and specificity of the SD-OCT’s significance maps for distinguishing early glaucoma were 95.0% and 94.4% when using either the uncorrected or the corrected mGCC. In 39 highly myopic eyes, the diagnostic accuracy was lower when using the uncorrected mGCC thickness (sensitivity was 95.2% and specificity was 44.4%), and was not improved when using the corrected mGCC (81.0% and 61.1%, respectively).

Conclusions:

The inferior mGCC was thinner in eyes with longer AL. The accuracy of the diagnosis with the SD-OCT built-in normative database for early glaucoma was not improved significantly by the correction of the AL-associated magnification in highly myopic eyes. Evaluation of highly myopic eyes with the nonhighly myopic normative database can lead to misdiagnosis.
Assessing the Role of the Family/Support System Perspective in Patients With Glaucoma
Authors: Shtein Roni M. , Newman-Casey Paula A. , Herndon Leon , Coleman Anne L. , Lee Paul P.
Published: November 2015

Purpose:

To investigate the role of the family/friends support system for patients with glaucoma and their perspective on barriers to effective glaucoma management.

Methods:

Six focus groups were conducted in 3 geographically and ethnically diverse areas of the United States (Los Angeles, CA; Rochester, MN; Durham, NC) that included 31 participants; 68% (21/31) were family members and friends of glaucoma patients with poor vision and 32% (10/31) were support system individuals of patients with good vision. Content analysis was used to identify important themes. Semiquantitative analysis was used to measure the frequency of each theme.

Results:

A total of 134 relevant comments were made in the 6 focus groups and 72% of relevant comments were made by individuals providing support for patients with poor vision. Family members and friends mentioned the following areas of concern regarding patients’ glaucoma care: patient education (19.4%), doctor-patient relationship (17.9%), their own lack of involvement in the patient’s medical care (17.2%), frustration with glaucoma and with the patient (14.9%), patient dependency on caregivers (14.9%), patient frustration with the disease (10.4%), and sex differences in coping mechanisms (5.2%).

Conclusions:

Support system individuals tend to be minimally involved in the patient’s glaucoma status and care. This is especially true for support system members of patients with glaucoma who maintain good vision and those who do not have any other personal experiences with difficulties from glaucoma. Many of these family members express an interest in acquiring more education about glaucoma and becoming more involved in the patient’s glaucoma care.
Outcomes of Nd:YAG Goniopuncture After Viscocanalostomy/Phacoviscocanalostomy
Authors: Mathews Divya , Shirodkar Amy-lee , Ahnood Dana , Garrick Adesuwa
Published: November 2015

Purpose:

The aim of this study is to evaluate the safety and efficacy of laser goniopuncture (LGP) to lower intraocular pressure (IOP) post-viscocanalostomy (VC)/phacoviscocanalostomy (PVC). Outcomes include: IOP reduction from pre-LGP levels and the need for further topical antiglaucomatous medication or surgery.

Patients and Methods:

A total of 541 eyes that underwent VC/PVC between 2009 and 2012, at the Stanley eye unit in Abergele were included in the study.

Inclusion criteria:

All patients who had LGP at any timepoint after VC/PVC when target IOP was not achieved +/− progression in visual field with at least 6 months of follow-up data.

Statistical analysis was performed on IOP values pre- and post-LGP, involving χ2, Fischer exact, Mann-Whitney U, and Wilcoxon tests. A P-value of <0.05 was accepted as the level of significance.

Results:

Of the 515 included eyes, 136 (26%) required LGP after a mean of 15.11±9.73 months after surgery (95% confidence interval, 13.46-16.76 mo), ranging from 1 to 42 months. LGP reduced IOP significantly from a mean of 22.92±5.80 to 17.08±5.30 mm Hg immediately for all eyes, a reduction of 5.84 mm Hg (or a 25% reduction) (P<0.0001). IOP significantly reduced in the VC group with a mean reduction of 7.60 mm Hg compared with 4.85 mm Hg in the PVC group immediately after the procedure (P=0.0038). LGP was required sooner in the VC group compared with PVC, 11.35 and 14.57 months, respectively (P=0.0393). A total of 69 (62%) eyes were commenced on topical IOP-lowering medications, mean 7.26±6.41 months after LGP.

Conclusions:

This study supports previous evidence that LGP enhances the IOP-lowering success of VC/PVC. The advantages of LGP are that it is a minimally invasive clinic-based procedure with a low complication rate.
Long-term Surgical Outcomes of 180-Degree Suture Trabeculotomy in Korean Patients With Primary Congenital Glaucoma
Authors: Park Ji-Hye , Yoo Chungkwon , Yoo Eunjoo , Kim Yong Yeon
Published: November 2015

Purpose:

To investigate the surgical outcomes of 180-degree suture trabeculotomy in Korean patients with primary congenital glaucoma (PCG).

Patients and Methods:

This retrospective study included 21 eyes of 17 children with PCG who underwent 180-degree suture trabeculotomy as a first surgical procedure. Surgical success was defined as (1) an intraocular pressure (IOP)<22 mm Hg with or without medication; (2) no additional intraocular surgery; and (3) no evidence of progressive optic disc cupping. The main outcome measure was the success rate of 180-degree suture trabeculotomy. Secondary outcome measures were IOP, number of glaucoma medications, and occurrence of complications.

Results:

Of the 21 eyes included, 18 (85.7%) were classified as having achieved success at the final visit (mean last follow-up or failure time, 54.91±45.68 mo). Median age at surgery was 11.97 months with mean IOP 29.8±9.6 mm Hg, on average of 1.52 medications. The mean IOP at the final visit was 16.9±5.6 mm Hg on an average of 0.38 medications. The surgical success rate of 180-degree suture trabeculotomy at 1, 3, and 5 years was 95.0%, 87.7%, and 78.9%, respectively (Kaplan-Meier analysis). Three eyes underwent second operations and the mean time to failure was 29.39±19.75 months. Hyphema was observed in 10 eyes, but it cleared up within 7.6 days.

Conclusion:

The 180-degree suture trabeculotomy performed for PCG had a significant IOP-lowering effect and caused no remarkable complications.
Management of Elevated Intraocular Pressure Associated With Subluxated/Dislocated Lenses by Combining Trabeculectomy With Adjunctive Mitomycin C With Lensectomy, Vitrectomy, and Scleral Fixation of Intraocular Lens
Authors: David Rathini L. , Balekudaru Shantha , George Ronnie J. , Sen Parveen , Lingam Vijaya
Published: November 2015

Aim:

To evaluate the short-term outcomes of lensectomy, combined with vitrectomy, scleral-fixated intraocular lens (SFIOL), and trabeculectomy with adjunctive mitomycin C (MMC) in patients with subluxated/dislocated crystalline lenses with associated elevated intraocular pressure (IOP).

Materials and Methods:

This retrospective case series included 51 eyes of 51 patients who underwent lensectomy, vitrectomy, and SFIOL combined with trabeculectomy with MMC between 2003 and 2012. The main outcome measures assessed were IOP, change in visual acuity, IOP-lowering medications, and the complications and reoperation rates.

Results:

The most common etiology observed was blunt trauma in 35 eyes (68.6%). Glaucomatous optic neuropathy was detected in 13 eyes (25.49%) preoperatively. The IOP reduced significantly from a preoperative mean of 26.3±11.5 mm Hg to 13±4.6 mm Hg (P<0.001) at the final visit. The mean preoperative number of IOP-lowering medications of 2.9±0.8 reduced to 0.3±0.7 at last follow-up (P<0.001). The best-corrected visual acuity (Snellens) improved significantly from 20/600 to 20/60 (P<0.001). Complete success defined as IOP≤21 mm Hg without medications was achieved in 93%±5% and 80%±13% at 1 and 2 years, respectively. Major postoperative complications included retinal detachment in one eye and SFIOL dislocation in another.

Conclusions:

The technique of combining SFIOLs with trabeculectomy with adjunctive MMC in the management of subluxated/dislocated lenses resulted in good IOP control and improvement in visual acuity.
The Effects of an Empowerment Intervention on Renal Transplant Recipients
Authors: Hsiao Chiu-Yueh , Lin Li-Wei , Su Yu-Wen , Yeh Shu-Hui , Lee Li-Na , Tsai Fu-Mian
Published: November 2015

Background:

Renal transplantation is a vital treatment for end-stage renal disease. To help improve quality of life after renal transplant surgery, interventions are needed to strengthen the coping skills and self-care behaviors of patients. However, most research studies on self-care after renal transplantation have addressed related factors. Few studies have examined the effects of interventions on renal transplant recipients.

Purpose:

This study investigated the effects of an empowerment support group on the empowerment levels and self-care behaviors of renal transplant recipients.

Methods:

This study was a randomized controlled trial. Eligible participants were individuals who had undergone a renal transplant within the past 20 years, were 18 years old or older, were able to read and write in Chinese, and were willing to participate. We recruited 122 renal transplant recipients from two medical centers in southern Taiwan. The renal transplant outpatients were randomly assigned into empowerment support (n = 56) and comparison (n = 66) groups. The developed measures as well as the content, protocols, and the two groups were assessed for reliability and validity. The intervention involved one 2-hour meeting every 2 weeks for a total of six meetings. The topics included goal setting, problem solving, coping with daily stress, seeking social support, and staying motivated. The sessions consisted of introductions that highlighted the topic, group discussions, identifying areas of difficulty with self-care behaviors after renal transplant, and developing a set of goals and strategies to overcome these problems.

Results:

The empowerment group reported significant increases both in terms of level of empowerment (F = 5.29, p = .023) based on age and time interaction (F = 9.86, p < .001) and in terms of self-care behaviors (F = 7.15, p = .009). Moreover, these increases were significantly larger than the increases recorded by the comparison group. In addition, these increases were particularly large in the older empowerment-group participants with lower pretest scores for empowerment.

Conclusions:

Empowerment support may be critical to improve the empowerment and self-care behaviors of renal transplant patients. The results of this study may be applied to improve patient education and empowerment programs for renal transplant patients. Furthermore, these programs may be adjusted to take into consideration the learning preferences or needs of different age groups.
Evolutionary history of the global emergence of the Escherichia coli epidemic clone ST131
Authors: Stoesser Nicole , Sheppard Anna , Pankhurst Louise , de Maio Nicola , Moore Catrin E , Sebra Robert , Turner Paul , Anson Luke W , Kasarskis Andrew , Batty Elizabeth M , Kos Veronica , Wilson Daniel J , Phetsouvanh Rattanaphone , Wyllie David , Sokurenko Evgeni , Manges Amee R , Johnson Timothy J , Price Lance B , Peto Timothy E. A. , Johnson James R , Didelot Xavier , Walker Ann Sarah , Crook Derrick W ,   Modernising Medical Microbiology Informatics Group
Published: November 2015

ABSTRACT Background Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. Results This study of the largest worldwide collection (n = 215) of sequenced ST131 E. coli isolates to date demonstrates that clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of a blaCTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids, and chromosomal integration of blaCTX-M within sub-clusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed amongst ST131, the blaCTX-M-14/14-like group. Conclusions The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli. These data also highlight the global imperative to reduce specific antibiotic selection pressures, and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages.
What’s in my pot? Real-time species identification on the MinION™
Authors: Juul Sissel , Izquierdo Fernando , Hurst Adam , Dai Xiaoguang , Wright Amber , Kulesha Eugene , Pettett Roger , Turner Daniel J.
Published: November 2015

Whole genome sequencing on next-generation instruments provides an unbiased way to identify the organisms present in complex metagenomic samples. However, the time-to-result can be protracted because of fixed-time sequencing runs and cumbersome bioinformatics workflows. This limits the utility of the approach in settings where rapid species identification is crucial, such as in the quality control of food-chain components, or in during an outbreak of an infectious disease. Here we present What’s in my Pot? (WIMP), a laboratory and analysis workflow in which, starting with an unprocessed sample, sequence data is generated and bacteria, viruses and fungi present in the sample are classified to subspecies and strain level in a quantitative manner, without prior knowledge of the sample composition, in approximately 3.5 hours. This workflow relies on the combination of Oxford Nanopore Technologies’ MinION™ sensing device with a real-time species identification bioinformatics application.
Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes
Authors: Kariuki Silvia N. , Blischak John D. , Nakagome Shigeki , Witonsky David B. , Di Rienzo Anna
Published: November 2015

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), plays an important immunomodulatory role, regulating transcription of genes in the innate and adaptive immune system. The present study examines patterns of transcriptome-wide response to 1,25D and the bacterial lipopolysaccharide (LPS) in primary human monocytes, to elucidate pathways underlying the effects of 1,25D on the immune system. Monocytes obtained from healthy individuals of African-African and European-American ancestry were treated with 1,25D alone or in the presence of LPS, which induced significant up-regulation of genes in the antimicrobial and autophagy pathways, while pro-inflammatory response genes were significantly down-regulated. A joint Bayesian analysis enabled clustering of genes into patterns of shared transcriptional response across treatments. The biological pathways enriched within these expression patterns highlighted several mechanisms through which 1,25D could exert its immunomodulatory role. Pathways such as mTOR signaling, EIF2 signaling, IL-8 signaling and Tec Kinase signaling were enriched among genes with opposite transcriptional responses to 1,25D and LPS, respectively, highlighting the important roles of these pathways in mediating the immunomodulatory activity of 1,25D. Furthermore, a subset of genes with evidence of inter-ethnic differences in transcriptional response was also identified, suggesting that in addition to the well-established inter-ethnic variation in circulating levels of vitamin D, the intensity of transcriptional response to 1,25D and LPS also varies between ethnic groups. We propose that dysregulation of the pathways identified in this study could contribute to immune-mediated disease risk.
Convergent patterns of sex chromosome dosage compensation between lepidopteran species (WZ/ZZ) and eutherian mammals (XX/XY): insights from a moth neo-Z chromosome
Authors: Gu Liuqi , Walters James R. , Knipple Douglas C.
Published: November 2015

In contrast to XX/XY species, Z-linked expression is overall reduced in female WZ/ZZ species compared to males or the autosomal expression. This pattern (Z<ZZ≈AA) has been consistently reported in all the WZ/ZZ taxa examined so far, with the singular exception of the insect order of Lepidoptera (moths and butterflies). However, conflicting results linger in this taxon due to discrepancies in data analyses and tissues sampled. To address this issue, we analyzed dosage compensation in the codling mothCydia pomonella(Tortricidae) using tissues that represent different levels of sexual divergence.C. pomonellais the most basal lepidopteran species yet examined for dosage compensation and has a neo-Z chromosome resulting from an ancient Z:autosome translocation. We based our analyses on RNAseq andde novotranscriptome data fromC. pomonella,as well as scrutiny into investigations of other lepidopteran species. Our evidence supports that the lepidopterans share a pattern (Z ≈ ZZ < AA) of dosage compensation that mirrors the eutherian mammals (X ≈ XX < AA). In particular, reproductive tissues appear to be exempt from dosage compensation, which helps explain the incongruence in prior reports. Furthermore,C. pomonellaancestral-Z segment exhibited a greater expression reduction than genes on the neo-Z segment, which intriguingly also reflects the differential up-regulation between the ancestral and newly-acquired X-linked genes in mammals. The insect order of Lepidoptera challenges both the classic theories regarding evolution of sex chromosome dosage compensation and the emerging view on dosage compensation’s association with sexual heterogamety.
Cannabis microbiome sequencing reveals several mycotoxic fungi native to dispensary grade cannabis flowers
Authors: McKernan Kevin , Spangler Jessica , Zhang Lei , Tadigotla Vasisht , Helbert Yvonne , Foss Theodore , Smith Douglas
Published: November 2015

The Center for Disease Control estimates 128,000 people in the U.S. are hospitalized annually due to food borne illnesses. This has created a demand for food safety testing targeting the detection of pathogenic mold and bacteria on agricultural products. This risk extends to medical Cannabis and is of particular concern with inhaled, vaporized and even concentrated Cannabis products. As a result, third party microbial testing has become a regulatory requirement in the medical and recreational Cannabis markets, yet knowledge of the Cannabis microbiome is limited. Here we describe the first next generation sequencing survey of the microbial communities found in dispensary based Cannabis flowers and demonstrate the limitations in the culture based regulations that are being superimposed from the food industry.
Using genotype data to distinguish pleiotropy from heterogeneity: deciphering coheritability in autoimmune and neuropsychiatric diseases
Authors: Han Buhm , Pouget Jennie G , Slowikowski Kamil , Stahl Eli , Lee Cue Hyunkyu , Diogo Dorothee , Hu Xinli , Park Yu Rang , Kim Eunji , Gregersen Peter K , Dahqvist Solbritt Rantapaa , Worthington Jane , Eyre Steve , Klareskog Lars , Huizinga Tom , Chen Wei-Min , Onengut-Gumuscu Suna , Rich Stephen S ,   Major Depressive Disorder Working Group of the PGC, Wray Naomi , Raychaudhuri Soumya
Published: November 2015

Shared genetic architecture between phenotypes may be driven by a common genetic basis (pleiotropy) or a subset of genetically similar individuals (heterogeneity). We developed BUHMBOX, a well-powered statistical method to distinguish pleiotropy from heterogeneity using genotype data. We observed a shared genetic basis between 11 of 17 tested autoimmune diseases and type I diabetes (T1D, p<10 12) and 11 of 17 tested autoimmune diseases and rheumatoid arthritis (RA, p<10-7). This sharing could not be explained by heterogeneity (corrected pBUHMBOX>0.2 using 6,670 T1D cases and 7,279 RA cases), suggesting that shared genetic features in autoimmunity are due to pleiotropy. We observed a shared genetic basis between seronegative and seropostive RA (p<10-22), explained by heterogeneity (pBUHMBOX=0.008 in 2,406 seronegative RA cases). Consistent with previous observations, we observed genetic sharing between major depressive disorder (MDD) and schizophrenia (p<10 9). This sharing is not explained by heterogeneity (pBUHMBOX=0.28 in 9,238 MDD cases).
Simulating serial-target antibacterial drug synergies using flux balance analysis
Authors: Krueger Andrew S. , Munck Christian , Dantas Gautam , Church George M. , Galagan James , Lehár Joseph , Sommer Morten O.A.
Published: November 2015

Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts can not predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity. However, we find very different predictions for combinations, where flux diversion, which mimics the kinetics of competitive metabolic inhibitors, can explain serial target synergies between metabolic enzyme inhibitors that we confirmed inEscherichia colicultures. FBA flux diversion opens the possibility for more accurate genome-scale predictions of drug synergies, which can be used to suggest treatments for infections and other diseases.
chopBAI: BAM index reduction solves I/O bottlenecks in the joint analysis of large sequencing cohorts
Authors: Kehr Birte , Melsted Páll
Published: November 2015

Advances in sequencing capacity have lead to the generation of unprecedented amounts of genomic data. The processing of this data frequently leads to I/O bottlenecks, e. g. when analyzing a small genomic region across a large number of samples. The largest I/O burden is, however, often not imposed by the amount of data needed for the analysis but rather by index files that help retrieving this data. We have developed chopBAI, a program that can chop a BAM index (BAI) file into small pieces. The program outputs a list of BAI files each indexing a specified genomic interval. The output files are much smaller in size but maintain compatibility with existing software tools. We show how preprocessing BAI files with chopBAI can lead to a reduction of I/O by more than 95% during the analysis of 10 Kbp genomic regions, eventually enabling the joint analysis of more than 10,000 individuals.

Availability and Implementation

The software is implemented in C++, GPL licensed and available athttp://github.com/DecodeGenetics/chopBAI
Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation
Authors: Neve Jonathan , Burger Kaspar , Li Wencheng , Hoque Mainul , Patel Radhika , Tian Bin , Gullerova Monika , Furger Andre
Published: November 2015

Alternative cleavage and polyadenylation (APA) plays a crucial role in the regulation of gene expression across eukaryotes. Although APA is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we used a rigorous subcellular fractionation approach to compare APA profiles of cytoplasmic and nuclear RNA fractions from human cell lines. This approach allowed us to extract APA isoforms that are subjected to differential regulation and provided us with a platform to interrogate the molecular regulatory pathways that shape APA profiles in different subcellular locations. Here, we show that APA isoforms with shorter 3′ UTRs tend to be overrepresented in the cytoplasm and appear to be cell-type–specific events. Nuclear retention of longer APA isoforms occurs and is partly a result of incomplete splicing contributing to the observed cytoplasmic bias of transcripts with shorter 3′ UTRs. We demonstrate that the endoribonuclease III, DICER1, contributes to the establishment of subcellular APA profiles not only by expected cytoplasmic miRNA-mediated destabilization of APA mRNA isoforms, but also by affecting polyadenylation site choice.
Spaces of Extraction, Metropolitan Explosions: Planetary Urbanization and the Commodity Boom in Latin America
Authors: Arboleda Martín
Published: November 2015

Through an exploration of the political economy of the current commodity boom in Latin America, and on the basis of recent appropriations of Henri Lefebvre's notion of planetary urbanization, this article proposes viewing spaces of resource extraction resulting from an escalating international demand for raw materials as particular morphological expressions of market‐driven processes of urbanization. Furthermore, the article draws on Lefebvre to argue that such burgeoning spaces of urbanization are the result of a contradictory tension between spatial homogenization—in the form of multiscalar governance frameworks and infrastructural programs—and territorial fragmentation—in the form of fixed capital allocations and state‐led spatial segregation. When considered jointly, these contradictory movements allow us to grasp fully the extent of the problematic explosion of spaces that, according to Lefebvre, characterizes capitalist urbanization. The article concludes by reflecting on the emancipatory promise that underlies the planetary extension of the urban form because, with the projection of material infrastructures required for resource extraction—especially information technologies—across the rural realm, local communities have been able to shed their isolated state and emerge as fully fledged political actors.