bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Nasal Valve Expanding Graft for Middle Vault Reconstruction
Authors: Aladag Ibrahim , Songu Murat , Aslan Hale , Imre Abdulkadir , Pinar Ercan
Published: February 2019

Various surgical techniques and approaches for addressing nasal valve collapse have been described in the literature. Still, new techniques continue to be developed and old techniques continue to be improved upon. The aim of the present study was to validate the use of the internal nasal valve expanding graft for middle vault reconstruction and to review the authors’ experience using this technique. A total of 32 patients who underwent middle vault reconstruction were retrospective reviewed. Analysis using Visual Analogue Scale (VAS) and Nasal Obstruction Symptom Evaluation (NOSE)-scale was performed pre- and postoperatively. Visual Analogue Scale scores for nasal airflow per side were collected on a 10-point scale, with 1 indicating total obstruction and 10 indicating a perfect nasal airway. Nasal Obstruction Symptom Evaluation scale was used to assess nasal obstruction. Minimum follow-up period was 6 months after the operation. Pre- and postoperative VAS scores were used to assess degree of nasal valve collapse according to examination findings. It was significant that there was improvement in nasal valve collapse after surgery (P < 0.05). Based upon pre- and postoperative calculations made using NOSE scores, there was significant improvement regarding nasal blockage or congestion, troubled breathing and sleeping, and air through nose during exercise, respectively (P < 0.05). No complications in terms of septal perforation, hematoma, synechiae, or infection that required further intervention were noted at postoperative follow-ups. In conclusion, internal nasal valve expanding graft has now been shown to be successful for middle vault reconstruction in a group of appropriately selected patient.
Effectiveness of Autologous Fat Grafting in Scaring After Augmentation Rhinoplasty
Authors: Xu Jing , Jiang Banghong , Shen Yan
Published: February 2019

Background:

Augmentation rhinoplasty is a widely popularity operation in Asia, but capsular contracture and retractile scars formation are frequent negative consequences, due to various properties of the implants. Lots of studies have reported improvements in scars after autologous fat grafting, but the mechanisms are still unclear. The aim of this study is to verify whether autologous fat grafting could treat the scaring after augmentation rhinoplasty for both functional and aesthetic purposes.

Methods:

From January 2011 to May 2017, 9 patients (8 females and 1 male) who suffered capsular contracture and retractile scars after augmentation rhinoplasty were treated with autologous fat grafting in the department and these patients were discussed in this study. Preoperative examinations and postoperative follow-up included use of photo documentations and the patient and observer scar assessment scale (POSAS) at 12 to 24 months.

Results:

All 9 patients achieved nasal aesthetic and functional improvement, and reduction for pain, stiff, irregular, relief, and pliability (P < 0.05) in POSAS scores was statistically significant.

Conclusion:

Capsular contracture and retractile scar after augmentation rhinoplasty were severe complication for patients; autologous fat grafting is a minimally invasive and effective treatment for the scaring for both functional and aesthetic purposes.
Stafne Bone Defect Involving the Ascending Ramus
Authors: Lee Kevin C. , Yoon Angela J. , Philipone Elizabeth M. , Peters Scott M.
Published: February 2019

The Stafne bone defect (SBD) classically presents as a well-defined, radiolucent lesion in the molar-mandibular angle region beneath the level of the mandibular canal. Due in large part to this prototypical appearance, most cases of SBDs are radiographically diagnostic without the need for tissue biopsy. A diagnostic challenge may arise, however, when the SBD occurs in other locations in the mandible. The authors report a case of a 57-year-old male who presented with a SBD of the left ascending ramus. The lesion was found incidentally on a panoramic radiograph. Additional imaging studies confirmed a lingual concavity of the mandibular bone consistent with a SBD, and a retrospective study of the patient's records revealed the presence of the lesion 5 years prior without any radiographic alterations. To date, only 10 documented cases of an SBD involving the ascending ramus have been reported. The rarity of such a presentation may obscure the diagnosis and lead to unwarranted surgical procedures. It is important to recognize atypically located SBDs, because unlike other radiolucent lesions, imaging studies are diagnostic. With proper diagnosis, additional surgical procedures and any associated morbidities can be avoided.
Evaluation of Olfactory Sensation, Acoustic Rhinometry, and Quality of Life of the Patients With Nasal Septal Deviation
Authors: Güzelküçük Akay Hatice , Bayar Muluk Nuray , Inal Mikail , Şimşek Gökçe , Kiliç Rahmi
Published: February 2019

Objectives:

Nasal septum deviations are deformities that occur in the cartilage and bones of the septum. The aim of the present study is to evaluate the patients with septum deviation according to the acoustic rhinometry measurements in terms of changes in smell function and the effects on quality of life.

Methods:

Twenty patients with septum deviation between the ages18 to 75 years old and 20 subjects without septum deviation were included in the study. Control group consisted of the 20 subjects with no septal deviation. After ENT examinations, acoustic rhinometry measurements, the SF-36 quality of life scale, and the Brief Smell Identification Tests were applied to all patients. Type of septum deviation is classified according to Mladina classification by anterior rhinoscopy examination, nasal endoscopy, and paranasal computed tomography.

Results:

The study indicated that the most common deviation type was Mladina Type 3 (65%). Bilateral total smell score of the women in the septum straight group is significantly lower than the men in terms of total smell scores by gender (P < 0.05). The total smell score values in septum group were significantly lower than those of the control group (P < 0.05). According to the individual smell values, cinnamon, banana, and soap odors of the septum deviation group were seen to be significantly lower than the septum straight group (P < 0.05).

Conclusion:

The results of the study indicated that olfactory dysfunction occurs in patients with septum deviation. Therefore, treatment of septum deviation is necessary for the improvement of nasal obstruction besides the treatment of the smell dysfunction.
A Large Scalp Defect Coverage With Pedicled Free Flap Using the Wrist as a Free Flap Carrier
Authors: Ku Inhoe , Kim Taewoon , Choi Kyujin , Na Hyoungmin , Lee Janghyuk , Jeong Euicheol C.
Published: February 2019

The absence of an adequate recipient vessel for free flap pedicle anastomosis near local defect sites discourages surgeons from performing free flap transfers over the scalp because of the challenging neck dissection and the thrombogenic potential of vein grafts for pedicle elongation. We present a case in which a large scalp defect was successfully reconstructed using the wrist as a “free flap carrier,” which is an alternative method. A 78-year-old patient with a totally occluded common carotid artery presented to our clinic with a large scalp defect. Reconstruction of the scalp defect was performed in a 2-stage procedure. In the first stage, a free latissimus dorsi (LD) muscle flap was transferred to the defect site, and the pedicle anastomosis was held at the ipsilateral wrist to provide inflow and outflow of blood through the radial artery and vena comitante and cephalic vein that were anastomosed to the flap pedicle. After subsequent split-thickness skin graft, the elevated position of the arm was achieved using a splint and sutures for 3 weeks. In the second stage, the flap was divided, and an additional skin graft over the flap division site and radial artery repair with vein graft was performed. Successful coverage of the scalp defect was confirmed on postoperative day 14 of the second procedure with no complications.
Resurfacing Large Skin Defects of the Face and Neck by Optimizing the Utilization of Expanded Forehead Axial-Pattern Flap and Cervicofacial Local Flap
Authors: Chen Hongbo , Tian Jia
Published: February 2019

It is very common for plastic surgeons to experience faciocervical defect, which could be quite challenging and should be processed with a good result. Expanded local flap and expanded axial-pattern flap from the forehead are both applied widely in the reconstruction of faciocervical region. It is crucial to choose appropriate techniques and treat the deformities effectively in the clinical practice. This study presented a treatment strategy for a child with multiple unit deformities in the face and neck by integrating and fully utilizing the expanded forehead axial-pattern flap combined with 2 expanded cervicofacial local flaps.
Surgical Management of the Superior Lip as a Complement in Facial Features Remodeling Surgery
Authors: Di Maggio Marcelo , Dobarro Juan Cruz , Nazar Anchorena Joaquín
Published: February 2019

The lower 3rd of the face is an essential area to pay attention to achieve excellent results in facial features remodeling surgery (FFRS). Because of its importance in facial remodeling surgery, special care has been taken in upper lip procedures. A combination of treatments has been used for the upper lip, which include surgical and nonsurgical procedures, depending on the patient assessment. The authors use a subnasal lip lift when surgery is required. This study describes the use of lip lift in combination with FFRS.
Cerebrospinal Fluid Removal for Idiopathic Intracranial Hypertension: Less Cerebrospinal Fluid Is Best
Authors: Perloff Michael D. , Parikh Simy K. , Fiorito-Torres Franchesca , McAdams Matthew T. , Rayhill Melissa L.
Published: February 2019

Background:

Although lumbar punctures (LPs) are used for diagnostic evaluation in idiopathic intracranial hypertension (IIH), they can also provide relief from IIH-associated headache. Conversely, low-pressure headache secondary to LP can be debilitating. Low-volume cerebrospinal fluid (CSF) removal to a “high-normal” closing pressure (CP), approximately 18–20 cm H2O, may result in relief of IIH-associated headache with a lowered frequency of post-LP headache.

Methods:

We conducted a single-center retrospective analysis from 2011 to 2016 of patients who underwent fluoroscopic LPs aiming for high-normal CPs. Inclusion criteria were as follows: 1) pre-existing diagnosis of IIH, or opening pressure (OP) and clinical findings diagnostic for IIH; 2) height and weight recorded within 1 year; 3) documented LP data parameters; and 4) one week post-LP follow-up documenting whether headache was worse, unchanged, or better.

Results:

One hundred forty-six patients met the inclusion criteria. Mean age was 34.9 years ± 11.0, and mean body mass index was 39.2 kg/m2 ± 10.5. Mean volume removed was 9.7 mL ± 4.6. The mean CP was 17.9 cm H2O ±2.7. The mean pressure change (OP-CP) per volume removed was 1.50 cm H2O/mL ±0.6. Headache symptoms at follow-up were improved in 64% (80/125) of patients, worse in 26% (33/125), and unchanged in 10% (12/125). Eleven patients were headache-free, and 11 patients required hospital care for post-LP headache.

Conclusions:

Low-volume CSF removal to approximately 18 cm H2O resulted in relief of IIH-associated headache in most patients and a low incidence of post-LP headache. Although clinically variable, these data suggest that for every 1 mL of CSF removed, the CP decreases approximately 1.5 cm H2O.
The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis
Authors: Koyano Takayuki , Namba Masumi , Kobayashi Tomoe , Nakakuni Kyomi , Nakano Daisuke , Fukushima Masaki , Nishiyama Akira , Matsuyama Makoto
Published: February 2019

Renal fibrosis is accompanied with the progression of chronic kidney disease (CKD). Despite a number of past and ongoing studies, our understanding of the underlying mechanisms remains elusive. Here we explored the progression of renal fibrosis by using a mouse model, unilateral ureter obstruction (UUO). We found that in the initial stage of the progression where extracellular matrix did not deposit yet, the proximal tubular cells arrested at the G2 of the cell cycle. This G2 arrest was induced prior to activation of both DNA damage checkpoint and Wnt/β-Catenin pathway. Further analyses in vivo and in vitro indicated the cyclin dependent kinase inhibitor p21 is involved in the G2 arrest after the damage. The newly produced monoclonal antibody against p21 revealed that the p21 levels were sharply upregulated in response to the damage during the initial stage, but dropped down toward the later stage. To examine the function of p21 in the progression of renal fibrosis, we constructed the novel p21 deficient mice by i-GONAD. Compared with wild-type mice, p21 deficient mice showed the exacerbation of the fibrosis. Thus we propose that during the initial stage of the fibrosis following the renal damage, tubular cells arrest in the G2 phase depending on p21, thereby safeguarding the kidney functions.
The impact of protein architecture on adaptive evolution
Authors: Moutinho Ana Filipa , Fontes Trancoso Fernanda , Dutheil Julien Yann
Published: February 2019

Adaptive mutations play an important role in molecular evolution. However, the frequency and nature of these mutations at the intra-molecular level is poorly understood. To address this, we analysed the impact of protein architecture on the rate of adaptive substitutions, aiming to understand how protein biophysics influences fitness and adaptation. UsingDrosophila melanogasterandArabidopsis thalianapopulation genomics data, we fitted models of distribution of fitness effects and estimated the rate of adaptive amino-acid substitutions both at the protein and amino-acid residue level. We performed a comprehensive analysis covering genome, gene and protein structure, by exploring a multitude of factors with a plausible impact on the rate of adaptive evolution, such as intron number, protein length, secondary structure, relative solvent accessibility, intrinsic protein disorder, chaperone affinity, gene expression, protein function and protein-protein interactions. We found that the relative solvent accessibility is a major driver of adaptive evolution, with most adaptive mutations occurring at the surface of proteins. Moreover, we observe that the rate of adaptive substitutions differs between protein functional classes, with genes encoding for protein biosynthesis and degradation signalling exhibiting the fastest rates of protein adaptation. Overall, our results suggest that adaptive evolution in proteins is mainly driven by inter-molecular interactions, with host-pathogen coevolution likely playing a major role.
Measuring single cell divisions in human cancers from multi-region sequencing data
Authors: Werner Benjamin , Case Jack , Williams Marc J. , Chkhaidze Kate , Temko Daniel , Fernandez-Mateos Javier , Cresswell George D. , Nichol Daniel , Cross William , Spiteri Inmaculada , Huang Weini , Tomlinson Ian , Barnes Chris P. , Graham Trevor A. , Sottoriva Andrea
Published: February 2019

Cancer is driven by complex evolutionary dynamics involving billions of cells. Increasing effort has been dedicated to sequence single tumour cells, but obtaining robust measurements remains challenging. Here we show that multi-region sequencing of bulk tumour samples contains quantitative information on single-cell divisions that is accessible if combined with evolutionary theory. Using high-throughput data from 16 human cancers, we measured thein vivoper-cell point mutation rate (mean: 1.69×10−8bp per cell division) and per-cell survival rate (mean: 0.57) in individual patient tumours from colon, lung and renal cancers. Per-cell mutation rates varied 50-fold between individuals, and per-cell survival rates were between nearly-homeostatic and almost perfect cell doublings, equating to tumour ages between 1 and 19 years. Furthermore, reanalysing a recent dataset of 89 whole-genome sequenced healthy haematopoietic stem cells, we find 1.14 mutations per genome per cell division and near perfect cell doublings (per-cell survival rate: 0.96) during early haematopoietic development. Our analysis measuresin vivothe most fundamental properties of human cancer and healthy somatic evolution at single-cell resolution within single individuals.
Differences in resources use lead to coexistence of seed-transmitted microbial populations
Authors: Torres-Cortés G , Garcia BJ , Compant S , Rezki S , Jones P , Préveaux A , Briand M , Roulet A , Bouchez O , Jacobson D , Barret M
Published: February 2019

Seeds are involved in the vertical transmission of microorganisms in plants and act as reservoirs for the plant microbiome. They could serve as carriers of pathogens, making the study of microbial interactions on seeds important in the emergence of plant diseases. We studied the influence of biological disturbances caused by seed transmission of two phytopathogenic agents,Alternaria brassicicolaAbra43 (Abra43) andXanthomonas campestrispv.campestris8004 (Xcc8004), on the structure and function of radish seed microbial assemblages, as well as the nutritional overlap between Xcc8004 and the seed microbiome, to find seed microbial residents capable of outcompeting this pathogen. According to taxonomic and functional inference performed on metagenomics reads, no shift in structure and function of the seed microbiome was observed following Abra43 and Xcc8004 transmission. This lack of impact derives from a limited overlap in nutritional resources between Xcc8004 and the major bacterial populations of radish seeds. However, two native seed-associated bacterial strains belonging toStenotrophomonas rhizophiladisplayed a high overlap with Xcc8004 regarding the use of resources; they might therefore limit its transmission. The strategy we used may serve as a foundation for the selection of seed indigenous bacterial strains that could limit seed transmission of pathogens.
Epigenetic inheritance of centromere identity in a heterologous system
Authors: Roure Virginie , Medina-Pritchard Bethan , Anselm Eduard , Arockia Jeyaprakash A. , Heun Patrick
Published: February 2019

The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, CENP-A, yet how its self-propagation is achieved remains poorly understood. Here we developed a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify the components required for dCENP-C loading onto chromatin, involving a cooperation between CAL1 and dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three Drosophila factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of centromere identity.
BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cell lines
Authors: Janssen Sanne Marlijn , Moscona Roy , Elchebly Mounib , Papadakis Andreas Ioannis , Redpath Margaret , Wang Hangjun , Rubin Eitan , van Kempen Léon Cornelis , Spatz Alan
Published: February 2019

Melanoma is among the most aggressive cancers due to its tendency to metastasize early. Phenotype switching between a proliferative and an invasive state has been suggested as a critical process for metastasis. The mechanisms that regulate these transitions are poorly understood, but are associated with transcriptional changes. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcriptional modulator that becomes aberrantly expressed in melanoma. Here, we provide the first evidence that BORIS is involved in phenotype switching in melanoma. Genetic modification of BORIS expression in melanoma cells combined with whole transcriptome analysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In agreement with this finding, inducible BORIS overexpression in melanoma cells reduced proliferation and increased migration and invasion, demonstrating that the transcriptional switch is accompanied by a phenotypic switch. Overall, our study indicates a pro-invasive role for BORIS in melanoma via transcriptional reprogramming.
An Omentum-inspired 3D PEG Hydrogel for Identifying ECM-drivers of Drug Resistant Ovarian Cancer
Authors: Brooks Elizabeth A. , Gencoglu Maria F. , Corbett Daniel C. , Stevens Kelly R. , Peyton Shelly R.
Published: February 2019

Ovarian cancer (OvCa) is a challenging disease to treat due to poor screening techniques and late diagnosis. There is an urgent need for additional therapy options, as patients recur in 70% of cases. The limited availability of clinical treatment options could be a result of poor predictions in early stage drug screens on standard tissue culture polystyrene (TCPS). TCPS does not capture the mechanical and biochemical cues that cells experiencein vivo, which can impact how cells will respond to a drug. Therefore, anin vitromodel that captures some of the microenvironment features that the cells experiencein vivocould provide better insights into drug response. In this study, we formed 3D multicellular tumor spheroids (MCTS) in microwells, and encapsulated them in 3D omentum-inspired hydrogels. SKOV-3 MCTS were resistant to Paclitaxel in our 3D hydrogels compared to a monolayer on TCPS. Toward clinical application, we tested cells from patients (ovarian carcinoma ascites spheroids (OCAS)), and drug responses predicted by using the 3D omentum-inspired hydrogels correlated with the reported pathology reports of those same patients. Additionally, we observed the presence of collagen production around the encapsulated SKOV-3 MCTS, but not on TCPS. Our results demonstrated that our 3D omentum-inspired hydrogel is an improvedin vitrodrug testing platform to study OvCa drug response for patient-derived cells, and helped us identify collagen 3 as a potential driver of Paclitaxel resistance.
Samovar: Single-sample mosaic SNV calling with linked reads
Authors: Darby Charlotte A. , Fitch James R. , Brennan Patrick J. , Kelly Benjamin J. , Bir Natalie , Magrini Vincent , Leonard Jeffrey , Cottrell Catherine E. , Gastier-Foster Julie M. , Wilson Richard K. , Mardis Elaine R. , White Peter , Langmead Ben , Schatz Michael C.
Published: February 2019

We present Samovar, a mosaic single-nucleotide variant (SNV) caller for linked-read whole-genome shotgun sequencing data. Samovar scores candidate sites using a random forest model trained using the input dataset that considers read quality, phasing, and linked-read characteristics. We show Samovar calls mosaic SNVs within a single sample with accuracy comparable to what previously required trios or matched tumor/normal pairs and outperform single-sample mosaic variant callers at MAF 5%-50% with at least 30x coverage. Furthermore, we use Samovar to find somatic variants in whole genome sequencing of both tumor and normal from 13 pediatric cancer cases that can be corroborated with high recall with whole exome sequencing. Samovar is available open-source at https://github.com/cdarby/samovar under the MIT license.
Task-evoked activity quenches neural correlations and variability across cortical areas
Authors: Ito Takuya , Brincat Scott L. , Siegel Markus , Mill Ravi D. , He Biyu J. , Miller Earl K. , Rotstein Horacio G. , Cole Michael W.
Published: February 2019

Many large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhancing their information coding by suppressing shared spontaneous activity. Here we sought to adjudicate between these conflicting perspectives, assessing whether co-active brain regions during task states tend to increase or decrease their correlations. We found that variability and correlations primarily decrease across a variety of cortical regions in two highly distinct data sets: non-human primate spiking data and human functional magnetic resonance imaging data. Moreover, this observed variability and correlation reduction was accompanied by an overall increase in dimensionality (reflecting less information redundancy) during task states, suggesting that decreased correlations increased information coding capacity. We further found in both spiking and neural mass computational models that task-evoked activity increased the stability around a stable attractor, globally quenching neural variability and correlations. Together, our results provide an integrative mechanistic account that encompasses measures of large-scale neural activity, variability, and correlations during resting and task states.
Undiagnosed and diagnosed hypertension in a community setting at Hosanna town: Uncovering the burden
Authors: Dereje Nebiyu , Earsido Alemu , Abebe Ashenafi , Temam Layla
Published: February 2019

Background

Hypertension is a leading cause of cardio-vascular diseases and its attributed mortality. No previous study, however, assessed the prevalence and associated factors of hypertension in the study area.

Methods

We recruited a representative sample of 627 adult individuals from selected kebeles of Hosanna town. A multi-stage sampling technique was employed in the study. A structured questionnaire using the WHO STEPS approach was employed to conduct a face to face interview and physical measurements. For each participant, we measured blood pressure two times after giving 10 minutes breaks between the measurements and we took the average. Hypertension status was defined as “systolic blood pressure ≥140mmhg and/or diastolic blood pressure ≥90mmhg”. Undiagnosed hypertension was defined as participants who had raised blood pressure on measurement, but not aware of it before. We used Multivariable logistic regression model to determine factors associated with hypertension.

Results

The overall prevalence of hypertension was found to be 17.2% (95% CI 14.5 – 19.9), 19.3% among men and 14.2% among women, of which 10.2% were unaware of it before. Hypertension was significantly associated with old age ≥35 years, excess alcohol intake, consumption of saturated oil/fat), consumption of unspecified different types of oil/fat and overweight/obesity.

Conclusion

The prevalence of hypertension (both diagnosed and undiagnosed) in the town is unacceptably high. This is also related to modifiable risk factors like excessive alcohol intake, overweight/obesity and consumption of saturated fat/oil. Therefore, designing health information provision systems on the risk factors of hypertension and promotion of good health practices should be considered. Moreover, the health departments should facilitate blood pressure screening programs at community levels to identify and treat undiagnosed hypertension.
Taxonomic survey ofAnadenobolus monilicornisgut microbiota via shotgun nanopore sequencing
Authors: Geli-Cruz Orlando J. , Cafaro Matias J. , Santos-Flores Carlos J. , Ropelewski Alex J. , Van Dam Alex R.
Published: February 2019

Millipedes constitute one of many soil-inhabiting organisms that act as important components of litter decomposition and nutrient recycling in terrestrial ecosystems. This is thanks in part to the microbial diversity that they contain in their gut compartments. However, millipedes and their gut microbiota are understudied, compared to other arthropods. For this reason, we partook in a metagenomic analysis of the gut ofAnadenobolus monilicornis. We collected specimens ofA. monilicornis, which were starved for a varying amount of time, from different municipalities of Puerto Rico. Once the DNA from their guts was extracted and sequenced using the MinION nanopore sequencer, we proceeded to analyze and compile the data obtained from the sequencer using programs such as Phylosift and MEGAN6 and the web-based MG-RAST. From our two best samples, we obtained a total of 87,110 and 99,749 reads, respectively. After comparing the data analyses and gene annotation done for both samples, we found that the bacterial phyla Proteobacteria, Bacteroidetes and Firmicutes were consistently well represented; one of our samples had much more Chlamydiae representation than the other, however. Sampled eukaryote phyla include Arthropoda, Chordata and Streptophyta. We would need a greater sample size to better determine differences in microbial diversity between millipede populations across the island; considering our small sample size, however, we were able to broadly reveal the diversity within the microenvironment ofA. monilicornis’s gut.
Leaf Variegation and Impaired Chloroplast Development Caused by a Truncated CCT Domain gene inalbostriansBarley
Authors: Li Mingjiu , Hensel Goetz , Mascher Martin , Melzer Michael , Budhagatapalli Nagaveni , Rutten Twan , Himmelbach Axel , Beier Sebastian , Korzun Viktor , Kumlehn Jochen , Börner Thomas , Stein Nils
Published: February 2019

Chloroplasts fuel plant development and growth by converting solar into chemical energy. They mature from proplastids through the concerted action of genes in both the organellar and the nuclear genome. Defects in such genes impair chloroplast development and may lead to pigment-deficient seedlings or seedlings with variegated leaves. Such mutants are instrumental as tools for dissecting genetic factors underlying the mechanisms involved in chloroplast biogenesis. Characterization of the green-white variegatedalbostriansmutant of barley has greatly broadened the field of chloroplast biology including the discovery of retrograde signaling. Here, we report the identification of theALBOSTRIANSgeneHvASTby positional cloning as well as its functional validation based on independently induced mutants by TILLING and RNA-guided Cas9 endonuclease mediated gene editing. The phenotypes of the independentHvASTmutants imply residual activity of HvAST in the originalalbostriansallele conferring an imperfect penetrance of the variegated phenotype even at homozygous state of the mutation.HvASTis a homolog of theArabidopsis thaliana CCT Motiftranscription factor geneAtCIA2, which was reported to be involved in the expression of nuclear genes essential for chloroplast biogenesis. Interestingly, in barley we localized HvAST to the chloroplast indicating novel without any clear evidence of nuclear localization.

One-sentence summary

Leaf variegation in the barley mutantalbostriansis caused by mutation of a single CCT-domain containing gene with residual activity, which is directed to the chloroplast.
Reconstruction of clone- and haplotype-specific cancer genome karyotypes from bulk tumor samples
Authors: Aganezov Sergey , Raphael Benjamin J.
Published: February 2019

Many cancer genomes are extensively rearranged with highly aberrant chromosomal karyotypes. These genome rearrangements, or structural variants, can be detected in tumor DNA sequencing data by abnormal mapping of se-quence reads to the reference genome. However, nearly all cancer sequencing to date is of bulk tumor samples which consist of a heterogeneous mixture of normal cells and subpopulations of cancers cells, or clones, that harbor distinct somatic structural variants. We introduce a novel algorithm,ReconstructingCancerKaryotypes (RCK), to reconstruct haplotype-specific karyotypes of one or more rearranged cancer genomes, or clones, that best explain the read alignments from a bulk tumor sample.RCKleverages specific evolutionary constraints on the somatic mutation process in cancer to reduce ambiguity in the deconvolution of admixed DNA sequence data into multiple haplotype-specific cancer karyotypes. In particular,RCKrelies on generalizations of the infinite sites assumption that a genome re-arrangement is highly unlikely to occur at the same nucleotide position more than once during somatic evolution.RCK’s comprehensive model allows us to incorporate information both from short and long-read sequencing technologies and is applicable to bulk tumor samples containing a mixture of an arbitrary number of derived genomes. We comparedRCKto the state-of-the-art methodReMixTon a dataset of 17 primary and metastatic prostate cancer samples. We demonstrate thatReMixT’s limited support for heterogeneity and lack of evolutionary constrains leads to reconstruction of implausible karyotypes. In contrast,RCK’s infers cancer karyotypes that better explain read alignments from bulk tumor samples and are consistent with a reasonable evolutionary model.RCK’s reconstructions of clone- and haplotype-specific karyotypes will aid further studies of the role of intra-tumor heterogeneity in cancer development and response to treatment.RCKis available athttps://github.com/raphael-group/RCK.
Inferring active cis-regulatory modules to predict functional regulatory elements
Authors: Chen Xi , Neuwald Andrew F. , Hilakivi-Clarke Leena , Clarke Robert , Xuan Jianhua
Published: February 2019

Transcription factors (TFs) often function as cis-regulatory modules (CRMs) including both master factors and mediator coactivators to activate enhancers or promoters and regulate target gene transcription. Cell type-specific ChIP-seq profiling of multiple TFs makes it feasible to infer functional CRMs for a particular cell type. Yet, approaches based on co-localization of TF ChIP-seq peaks to infer CRMs are applied but many weak binding events, especially of those mediators, are missed by peak callers, resulting in an incomplete identification of CRMs. We developed a ChIP-seq data-based CRM inference approach with Gibbs-Sampling (ChIP-GSM). In a Bayesian framework, ChIP-GSM samples read counts of TFs iteratively for the joint effect of each potential TF combination. Using inferred CRMs as novel features, ChIP-GSM employs a logistic regression model to predict active regulatory elements. Performance validation on FANTOM5 enhancer or promoter regions revealed the superior performance of CRMs on regulatory region activity prediction than TFs. Finally, integrating CRMs inferred for K562 cells and gene expression data we found that CRMs are likely to activate regulatory regions or genes at different time points to mediate distinct cellular functions.

Author Summary

Accurately inferring cis-regulatory modules (CRMs) from a large set of TFs is a challenging task because the binding signals of TFs are often weak, noisy and sensitive to the cellular environment. Nevertheless, investigating TF associations may help understand the difference between enhancer and promoter activation mechanisms. In this paper, we develop a computational method (ChIP-GSM) to infer CRMs acting on regulatory elements at enhancer and promote regions. The novel method is built upon a Bayesian framework with Gibbs sampling that can be used to infer CRMs reliably hence to predict regulatory elements. The performance of ChIP-GSM is compared to that of existing methods, demonstrating its improved performance. Experimental results demonstrate that CRMs identified by ChIP-GSM are likely activating regulatory regions at different time points to mediate distinct cellular functions.
A genome-wide screen for ER autophagy highlights key roles of mitochondrial metabolism and ER-resident UFMylation
Authors: Liang Jin Rui , Lingeman Emily , Luong Thao , Ahmed Saba , Nguyen Truc , Olzmann James , Corn Jacob E.
Published: February 2019

Selective degradation of organelles via autophagy is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few specialized autophagosomal receptors and remodelers. Using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence factors involved in human ER-phagy. We mechanistically investigated two pathways unexpectedly required for ER-phagy. First, reduced mitochondrial metabolism represses ER-phagy, which reverses the logic of general autophagy. Mitochondrial crosstalk with ER-phagy bypasses the energy sensor AMPK, instead directly impacting ULK1. Second, ER-localized UFMylation is required for ER-phagy that represses the unfolded protein response. The UFL1 ligase is brought to the ER surface by DDRGK1, analogous to PINK1-Parkin regulation during mitophagy. Our data provide insight into the unique cellular logic of ER-phagy, reveal parallels between organelle autophagies, and provide an entry point to the relatively unexplored process of degrading the ER network.
Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme
Authors: Carpenedo Richard L , Kwon Sarah Y , Tanner R Matthew , Yockell-Lelièvre Julien , Choey Chandarong , Doré Carole , Ho Mirabelle , Stewart Duncan J , Perkins Theodore J , Stanford William L
Published: February 2019

Human pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.
Intra-mitochondrial proteostasis is directly coupled to alpha-synuclein and Amyloid β 1-42 pathology
Authors: Lautenschläger Janin , Wagner-Valladolid Sara , Stephens Amberley D. , Fernández-Villegas Ana , Hockings Colin , Mishra Ajay , Manton James D. , Fantham Marcus J. , Lu Meng , Rees Eric J. , Kaminski Clemens F. , Schierle Gabriele S. Kaminski
Published: February 2019

Mitochondria have long been implicated in Parkinson’s disease (PD), however, it is not clear how mitochondrial impairment and alpha-synuclein pathology are coupled. We report here that intra-mitochondrial protein homeostasis plays a major role in alpha-synuclein fibril elongation, as interference with intra-mitochondrial proteases and mitochondrial protein import significantly aggravate alpha-synuclein aggregation. In contrast, direct inhibition of mitochondrial complex I, increase in intracellular calcium concentration or formation of reactive oxygen species (ROS), all of which have been associated with mitochondrial stress, did not affect alpha-synuclein pathology. We further demonstrate that similar mechanisms are involved in Amyloid β 1-42 (Aβ42) aggregation, suggesting that mitochondria are directly capable of influencing cytosolic protein homeostasis of aggregation-prone proteins.
Pair-wise Comparison Analysis for Multiple Pool-seq: an efficient method identified anthocyanin biosynthesis genes in rice pericarp
Authors: Yang Xinghai , Xia Xiuzhong , Zhang Zongqiong , Nong Baoxuan , Zeng Yu , Wu Yanyan , Xiong Faqian , Zhang Yuexiong , Liang Haifu , Pan Yinghua , Dai Gaoxing , Deng Guofu , Li Danting
Published: February 2019

The complex traits are derived from multiple genes and exhibit a large variety of phenotypes. High-throughput sequencing technologies have become the new strategies for mapping the important traits of crops. However, these methods have their own disadvantages and limitations. Here we introduced Pair-wise Comparison Analysis for Multiple Pool-seq (PCAMP) for mapping the candidate genomic regions involved in anthocyanin biosynthesis in rice pericarp. In this protocol, the second filial generation (F2) populations obtained by crossing two parents with different target traits were divided into n (n>=3) subpopulations according to their phenotypes. Thirty phenotypically identical individuals were selected from each subpopulation and DNA samples were extracted to form a pool for sequencing. Finally, we compared the SNP-index between every two Pool-seqs to map the candidate genomic regions. We applied PCAMP to analyse F2populations and successfully identified five known genes and five new candidate genomic regions for anthocyanin biosynthesis in rice pericarp. These results demonstrate that PCAMP is an efficient new method for dissecting the complex traits of crops.
Pharmacogenomics, biomarker network and allele frequencies in colorectal cancer
Authors: López-Cortés Andrés , Paz-y-Miño César , Guerrero Santiago , Jaramillo-Koupermann Gabriela , Intriago-Baldeón Dámaris P. , García-Cárdenas Jennyfer M. , Guevara-Ramírez Patricia , Armendáriz-Castillo Isaac , Leone Paola E. , Quiñones Luis Abel , Cayún Juan Pablo , Soria Néstor W.
Published: February 2019

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Over the last decades, several studies have shown that tumor-related genomic alterations predict tumor prognosis, drug response and toxicity. These observations have led to the development of a number of precision therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations that may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. Here we conduct a comprehensive review of the main pharmacogenomics biomarkers and genomic alterations affecting enzyme activity, transporter capacity, channels and receptors, and therefore the new advances in CRC precision medicine to select the best therapeutic strategy in populations worldwide, with a focus on Latin America.
Divisively normalized integration of multisensory error information develops motor memories specific to vision and proprioception
Authors: Hayashi Takuji , Kato Yutaro , Nozaki Daichi
Published: February 2019

Both visual and proprioceptive information contribute to accurate limb movement, but the mechanism of integration of these different modality signals for movement control and learning remains controversial. Here, we aimed to elucidate the mechanism of integration by examining motor adaptation when various combinations of visual and proprioceptive perturbations were applied during reaching movements. We found that the movement corrections by adaptation were explained by a mechanism known as a divisive normalization, which was previously reported to be the mechanism underlying the integration of multisensory signals in neurons. Furthermore, we found evidence that the motor memory for each sensory modality was formed separately and the outputs from these memories were integrated. These results provide a novel view of the utilization of different sensory modality signals in motor control and adaptation.
A Rab11-GEF Parcas recruits Rab11 onto recycling endosomes for rhodopsin transport in Drosophila photoreceptors
Authors: Otsuka Yuna , Satoh Takunori , Nakayama Nozomi , Inaba Ryota , Satoh Akiko Kono
Published: February 2019

Rab11 and its effectors dRip11 and MyoV are essential for polarized post-Golgi vesicle trafficking to photosensitive membrane rhabdomeres in Drosophila photoreceptors. Here, we found that Parcas (Pcs), recently shown to have guanine-nucleotide-exchange (GEF) activity toward Rab11, co-localizes with Rab11 on the trans-side of Golgi units and post-Golgi vesicles at the base of the rhabdomeres in pupal photoreceptors. Pcs fused with the EM-tag APEX2 localizes on 150-300 nm vesicles at the trans-side of Golgi units, which are presumably fly recycling endosomes (RE). Loss of Pcs impairs Rab11 localization on the trans-side of Golgi units and induces the cytoplasmic accumulation of post-Golgi vesicles bearing rhabdomere proteins, as observed in Rab11-deficiency. In contrast, loss of the specific subunits of TRAPPII, another known Rab11-GEF, does not cause any defects on the eye development nor the transport of rhabdomere proteins, however, simultaneous loss of TRAPPII and Pcs shows severe defects on eye development. These results indicated that in pupal photoreceptors, Pcs is the predominant Rab11-GEF, and TRAPPII performs a function that is redundant but subsidiary to that of Pcs.
xiView: A common platform for the downstream analysis of Crosslinking Mass Spectrometry data
Authors: Graham Martin , Combe Colin , Kolbowski Lars , Rappsilber Juri
Published: February 2019

xiView provides a common platform for the downstream analysis and visualisation of Crosslinking Mass Spectrometry data. It is independent of the search software used and its input is compliant with the relevant mass spectrometry data standards. It uses established visualisation techniques, notably Multiple Coordinated Views, to help the user explore the data and is designed to facilitate comparisons between different datasets.
Integrated approaches to identifying cryptic bat species in areas of high endemism: the case ofRhinolophus andamanensisin the Andaman Islands
Authors: Srinivasulu Chelmala , Srinivasulu Aditya , Srinivasulu Bhargavi , Jones Gareth
Published: February 2019

The diversity of bats worldwide includes large numbers of cryptic species, partly because divergence in acoustic traits such as echolocation calls are under stronger selection than differences in visual appearance in these nocturnal mammals. Island faunas often contain disproportionate numbers of endemic species, and hence we might expect cryptic, endemic species to be discovered relatively frequently in bats inhabiting islands. Species are best defined when multiple lines of evidence supports their diagnosis. Here we use morphometric, acoustic, and molecular phylogenetic data to show that a horseshoe bat in the Andaman Islands is distinct in all three aspects, supporting its description as a newly described endemic species. We recommend investigation into possible new and endemic bat species on islands by using integrated approaches that provide independent lines of evidence for taxonomic distinctiveness. We provide a formal description of the new species –Rhinolophus andamanensisDobson, 1872.