bluuebunny/crossref_metadata_2025 huggingface dataset:
Aesthetic Breast Surgery Under Cold Tumescent Anesthesia
Authors: Ceccarino Raffaele , Di Micco Rosa , Cappelletti Renato
Published: January 2019

Throughout the last decade, aesthetic breast surgery has enormously spread in the outpatient clinic setting where plastic surgeons perform the vast majority of procedures under local anesthesia as day-case operations. The “tumescent anesthesia” is defined as the injection of a dilute solution of local anesthetic combined with epinephrine and sodium bicarbonate into subcutaneous tissue until it becomes firm and tense, which is “tumescent.” The “cold tumescent anesthesia” (CTA) derives from Klein's solution with the introduction of a new concept, which is the low temperature (4°C) of the injected solution. This novelty adds further anesthetic and hemostatic power to the well-known benefits of tumescent anesthesia. The authors report their experience with CTA in the last 15 years in the setting of aesthetic breast surgery, describing in detail the anesthesia protocol, surgical outcomes, and patient satisfaction. A total of 1541 patients were operated on during the study period and were included in this retrospective analysis. The types of breast procedures were breast augmentation in 762 cases (49.4%), mastopexy with implants in 123 patients (8.0%), mastopexy without implants in 452 cases (29.3%), and breast reduction in 204 cases (13.3%). Patient mean age was 42.8 years (range, 18–67 years). The mean operating time was 37 ± 32 minutes for breast augmentation, 78 ± 24 minutes for mastopexy with implants, 58 ± 18 minutes for mastopexy without implants, and 95 ± 19 minutes for breast reduction. No major complications occurred, and no conversion to general anesthesia was required. The median recovery time was 150 minutes (range, 120–210 minutes), and all patients were discharged within 3 hours after surgery. Wound or implant infections occurred in 33 patients (2.1%), wound dehiscences in 21 (1.4%), and postoperative bleeding requiring return to theater in 2 cases (0.1%). Thirteen patients (0.8%) developed capsular contracture. Fifteen patients (1%) required reintervention due to implant rotation or rupture. The median visual analog scale score was 1.8 (interquartile range, 1–3) after discharge. Patient satisfaction was very high in 91.3% (n = 1407) of the cases. In experienced hands, CTA can shorten operating time with high patient satisfaction and a low complication rate. These preliminary data could be hypothesis generating for future multicenter prospective trials done to confirm the benefits of CTA in other surgical fields.
Timing But Not Patterns of Recurrence Is Different Between Node-negative and Node-positive Resected Pancreatic Cancer
Authors: Honselmann Kim C. , Pergolini Ilaria , Castillo Carlos Fernandez-del , Deshpande Vikram , Ting David , Taylor Martin S. , Bolm Louisa , Qadan Motaz , Wellner Ulrich , Sandini Marta , Bausch Dirk , Warshaw Andrew L. , Lillemoe Keith D. , Keck Tobias , Ferrone Cristina R.
Published: January 2019

Objective:

Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes.

Summary Background Data:

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues.

Methods:

Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152).

Results:

Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435).

Conclusion:

Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.
Laser-based Techniques for Microcirculatory Assessment in Orthopedics and Trauma Surgery
Authors: Rüwald Julian M. , Jacobs Cornelius , Scheidt Sebastian , Burger Christof , Wirtz Dieter C. , Schildberg Frank A.
Published: January 2019

Microcirculatory integrity and proper function are the cornerstones to tissue nourishment and viability. In the clinical environment extended immobility, injuries, and inflammatory reactions demand local microcirculatory adaption to provide adequate supply. Assessment of endothelial adjustment capability and microcirculatory perfusion status, as direct or surrogate markers of disease, are therefore of uttermost interest to the treating physician. Given the simple, noninvasive, nonradiating nature of laser-based techniques for bedside or intraoperative microcirculatory perfusion assessment, this article's objective is to present a comprehensive overview of available techniques, their technological aspects, and current application. Advantages of individual methods are pointed out and compared with each other. The areas of medical utilization relevant to orthopedics and trauma surgery are exemplified and their available evidence elaborated. A particular focus is put on laser speckle contrast imaging, with its current and future influence on medical practice.
Comparison of Outcomes After Partial Versus Complete Mesh Excision
Authors: Kao Angela M. , Arnold Michael R. , Otero Javier , Huang Li-Ching , Prasad Tanushree , Lincourt Amy E. , Augenstein Vedra A.
Published: January 2019

Objective:

Evaluate outcomes of patients undergoing mesh explantation following partial mesh excision (PME) and complete mesh excision (CME).

Background:

Ventral hernia repair (VHR) with mesh remains one of the most commonly performed procedures worldwide. Management of previously placed mesh during reexploration remains unclear. Studies describing PME as a feasible alternative have been limited.

Methods:

The AHSQC registry was queried for VHR patients who underwent mesh excision. Variables used for propensity-matching included age, BMI, race, diabetes, COPD, OR time>2 hours, immunosuppressants, smoking, active infection, ASA class, elective case, wound classification, and history of abdominal wall infection.

Results:

A total of 1904 VHR patients underwent excision of prior mesh. After propensity matching, complications were significantly higher (35% vs 29%, P = 0.01) after PME, including SSI/SSO, SSOPI, and reoperation. No differences were observed in patients with clean wounds, however in clean-contaminated, PME more frequently resulted in SSOPI (24% vs 9%, P = 0.02). In mesh infection/fistulas, higher rates of SSOPI (46% vs 24%, P = 0.04) and reoperation (21% vs 6%, P = 0.03) were seen after PME. Odds-ratio analysis showed increased likelihood of SSOPI (OR 1.5, 95% CI 1.05–2.14; P = 0.023) and reoperation (OR 2.2, 95% CI 1.13–4.10; P = 0.015) with PME.

Conclusions:

With over 350,000 VHR performed annually and increasing mesh use, guidelines for management of mesh during reexploration are needed. This analysis of a multicenter hernia database demonstrates significantly increased postoperative complications in PME patients with clean-contaminated wounds and mesh infections/fistulas, however showed similar outcomes in those with clean wounds.
Immunological signatures in frontotemporal lobar degeneration
Authors: Sirkis Daniel W. , Bonham Luke W. , Karch Celeste M. , Yokoyama Jennifer S.
Published: January 2019

Purpose of review

Over the last year, research into the immunological and inflammatory signatures of frontotemporal lobar degeneration (FTLD) has accelerated greatly. Herein, we highlight recently proposed roles of brain-resident microglia as well as peripheral myeloid cells in frontotemporal dementia (FTD)-spectrum disorders.

Recent findings

Recent unbiased genetic, transcriptomic, and proteomic surveys using human data confirm significantly altered immune-function genes as well as transcript and protein modules associated with inflammatory and immune function. Beyond human studies, novel animal models indicate important roles for both microglia and monocytes, and central involvement of genes such as Trem2, Apoe, and Tbk1.

The importance of neuroinflammatory activity in FTD pathophysiology is unambiguous, but whether this activity is primarily beneficial or detrimental remains unclear, with variable results reported for distinct disease paradigms. Going forward, it will be crucial to determine which types of microglial and peripheral myeloid responses are favorable, in response to which specific proteinopathies, and at which point in disease course.
Effects of cell morphology and attachment to a surface on the hydrodynamic performance of unicellular choanoflagellates
Authors: Nguyen Hoa , Koehl M. A. R. , Oakes Christian , Bustamante Greg , Fauci Lisa
Published: January 2019

Choanoflagellates, eukaryotes that are important predators on bacteria in aquatic ecosystems, are closely related to animals and are used as a model system to study the evolution of animals from protozoan ancestors. The choanoflagellate
Salpingoeca rosetta
has a complex life cycle with different morphotypes, some unicellular and some multicellular. Here we use computational fluid dynamics to study the hydrodynamics of swimming and feeding by different unicellular stages of
S. rosetta
: a swimming cell with a collar of prey-capturing microvilli surrounding a single flagellum, a thecate cell attached to a surface and a dispersal-stage cell with a slender body, long flagellum and short collar. We show that a longer flagellum increases swimming speed, longer microvilli reduce speed and cell shape only affects speed when the collar is very short. The flux of prey-carrying water into the collar capture zone is greater for swimming than sessile cells, but this advantage decreases with collar size. Stalk length has little effect on flux for sessile cells. We show that ignoring the collar, as earlier models have done, overestimates flux and greatly overestimates the benefit to feeding performance of swimming versus being attached, and of a longer stalk for attached cells.
Polarized skylight-based heading measurements: a bio-inspired approach
Authors: Dupeyroux Julien , Viollet Stéphane , Serres Julien R.
Published: January 2019

Many insects such as desert ants, crickets, locusts, dung beetles, bees and monarch butterflies have been found to extract their navigation cues from the regular pattern of the linearly polarized skylight. These species are equipped with ommatidia in the dorsal rim area of their compound eyes, which are sensitive to the angle of polarization of the skylight. In the polarization-based robotic vision, most of the sensors used so far comprise high-definition CCD or CMOS cameras topped with linear polarizers. Here, we present a 2-pixel polarization-sensitive visual sensor, which was strongly inspired by the dorsal rim area of desert ants' compound eyes, designed to determine the direction of polarization of the skylight. The spectral sensitivity of this minimalistic sensor, which requires no lenses, is in the ultraviolet range. Five different methods of computing the direction of polarization were implemented and tested here. Our own methods, theextendedandAntBotmethod, outperformed the other three, giving a mean angular error of only 0.62° ± 0.40° (median: 0.24°) and 0.69° ± 0.52° (median: 0.39°), respectively (mean ± standard deviation). The results obtained in outdoor field studies show that our celestial compass gives excellent results at a very low computational cost, which makes it highly suitable for autonomous outdoor navigation purposes.
Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis
Authors: Chen Bing , Xia Zijing , Deng Ya-Nan , Yang Yanfang , Zhang Peng , Zhu Hongxia , Xu Ningzhi , Liang Shufang
Published: January 2019

MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction. Along with analytical technique improvements in miRNA research, use of the emerging extracellular miRNAs is feasible for CRC diagnosis and prognosis.
Parent-preferred dispersal promotes cooperation in structured populations
Authors: Chen Xiaojie , Brännström Åke , Dieckmann Ulf
Published: January 2019

Dispersal is a key process for the emergence of social and biological behaviours. Yet, little attention has been paid to dispersal's effects on the evolution of cooperative behaviour in structured populations. To address this issue, we propose two new dispersal modes, parent-preferred and offspring-preferred dispersal, incorporate them into the birth–death update rule, and consider the resultant strategy evolution in the prisoner's dilemma on random-regular, small-world, and scale-free networks, respectively. We find that parent-preferred dispersal favours the evolution of cooperation in these different types of population structures, while offspring-preferred dispersal inhibits the evolution of cooperation in homogeneous populations. On scale-free networks when the strength of parent-preferred dispersal is weak, cooperation can be enhanced at intermediate strengths of offspring-preferred dispersal, and cooperators can coexist with defectors at high strengths of offspring-preferred dispersal. Moreover, our theoretical analysis based on the pair-approximation method corroborates the evolutionary outcomes on random-regular networks. We also incorporate the two new dispersal modes into three other update rules (death-birth, imitation, and pairwise comparison updating), and find that similar results about the effects of parent-preferred and offspring-preferred dispersal can again be observed in the aforementioned different types of population structures. Our work, thus, unveils robust effects of preferential dispersal modes on the evolution of cooperation in different interactive environments.
Bryophyte stable isotope composition, diversity and biomass define tropical montane cloud forest extent
Authors: Horwath Aline B. , Royles Jessica , Tito Richard , Gudiño José A. , Salazar Allen Noris , Farfan-Rios William , Rapp Joshua M. , Silman Miles R. , Malhi Yadvinder , Swamy Varun , Latorre Farfan Jean Paul , Griffiths Howard
Published: January 2019

Liverworts and mosses are a major component of the epiphyte flora of tropical montane forest ecosystems. Canopy access was used to analyse the distribution and vertical stratification of bryophyte epiphytes within tree crowns at nine forest sites across a 3400 m elevational gradient in Peru, from the Amazonian basin to the high Andes. The stable isotope compositions of bryophyte organic material (13C/12C and18O/16O) are associated with surface water diffusive limitations and, along with C/N content, provide a generic index for the extent of cloud immersion. From lowland to cloud forest δ13C increased from −33‰ to −27‰, while δ18O increased from 16.3‰ to 18.0‰. Epiphytic bryophyte and associated canopy soil biomass in the cloud immersion zone was estimated at up to 45 t dry mass ha−1, and overall water holding capacity was equivalent to a 20 mm precipitation event. The study emphasizes the importance of diverse bryophyte communities in sequestering carbon in threatened habitats, with stable isotope analysis allowing future elevational shifts in the cloud base associated with changes in climate to be tracked.
Conservation biology needs a microbial renaissance: a call for the consideration of host-associated microbiota in wildlife management practices
Authors: Trevelline Brian K. , Fontaine Samantha S. , Hartup Barry K. , Kohl Kevin D.
Published: January 2019

The central aim of conservation biology is to understand and mitigate the effects of human activities on biodiversity. To successfully achieve this objective, researchers must take an interdisciplinary approach that fully considers the effects, both direct and indirect, of anthropogenic disturbances on wildlife physiology and health. A recent surge in research has revealed that host-associated microbiota—the archaeal, bacterial, fungal and viral communities residing on and inside organisms—profoundly influence animal health, and that these microbial communities can be drastically altered by anthropogenic activities. Therefore, conservation practitioners should consider the disruption of host-associated microbial diversity as a serious threat to wildlife populations. Despite the tremendous potential for microbiome research to improve conservation outcomes, few efforts have been made to truly integrate these fields. In this review, we call for the microbial renaissance of conservation biology, where biodiversity of host-associated microbiota is recognized as an essential component of wildlife management practices. Using evidence from the existing literature, we will examine the known effects of anthropogenic activities on the diversity of host-associated microbial communities and integrate approaches for maintaining microbial diversity to successfully achieve conservation objectives.
Whole genome sequence analysis of Australian avian pathogenic Escherichia coli that carry the class 1 integrase gene
Authors: Cummins Max L. , Reid Cameron J. , Roy Chowdhury Piklu , Bushell Rhys N. , Esbert Nicolas , Tivendale Kelly A. , Noormohammadi Amir H. , Islam Shaiful , Marenda Marc S. , Browning Glenn F. , Markham Philip F. , Djordjevic Steven P.
Published: January 2019

Avian pathogenic

Escherichia coli

(APEC) cause widespread economic losses in poultry production and are potential zoonotic pathogens. Genome sequences of 95 APEC from commercial poultry operations in four Australian states that carried the class 1 integrase gene intI1, a proxy for multiple drug resistance (MDR), were characterized. Sequence types ST117 (22/95), ST350 (10/95), ST429 and ST57 (each 9/95), ST95 (8/95) and ST973 (7/95) dominated, while 24 STs were represented by one or two strains. FII and FIB repA genes were the predominant (each 93/95, 98 %) plasmid incompatibility groups identified, but those of B/O/K/Z (25/95, 26 %) and I1 (24/95, 25 %) were also identified frequently. Virulence-associated genes (VAGs) carried by ColV and ColBM virulence plasmids, including those encoding protectins [iss (91/95, 96 %), ompT (91/95, 96 %) and traT (90/95, 95 %)], iron-acquisition systems [sitA (88/95, 93 %), etsA (87/95, 92 %), iroN (84/95, 89 %) and iucD/iutA (84/95, 89 %)] and the putative avian haemolysin hylF (91/95, 96 %), featured prominently. Notably, mobile resistance genes conferring resistance to fluoroquinolones, colistin, extended-spectrum β-lactams and carbapenems were not detected in the genomes of these 95 APEC but carriage of the sulphonamide resistance gene, sul1 (59/95, 63 %), the trimethoprim resistance gene cassettes dfrA5 (48/95, 50 %) and dfrA1 (25/95, 27 %), the tetracycline resistance determinant tet(A) (51/95, 55 %) and the ampicillin resistance genes blaTEM-1A/B/C
(48/95, 52 %) was common. IS26 (77/95, 81 %), an insertion element known to capture and mobilize a wide spectrum of antimicrobial resistance genes, was also frequently identified. These studies provide a baseline snapshot of drug-resistant APEC in Australia and their role in the carriage of ColV-like virulence plasmids.
Cis-epistasis at the LPA locus and risk of coronary artery disease
Authors: Zeng Lingyao , Mirza-Schreiber Nazanin , Lamina Claudia , Coassin Stefan , Nelson Christopher P. , Franzén Oscar , Kleber Marcus E. , Mack Salome , Andlauer Till F. M. , Jiang Beibei , Stiller Barbara , Li Ling , Willenborg Christina , Munz Matthias , Kessler Thorsten , Kastrati Adnan , Laugwitz Karl-Ludwig , Erdmann Jeanette , Moebus Susanne , Nöthen Markus M. , Peters Annette , Strauch Konstantin , Müller-Nurasyid Martina , Gieger Christian , Meitinger Thomas , Steinhagen-Thiessen Elisabeth , März Winfried , Björkegren Johan L. M. , Samani Nilesh J. , Kronenberg Florian , Müller-Myhsok Bertram , Schunkert Heribert
Published: January 2019

Identification of epistasis affecting complex human traits has been challenging. Focusing on known coronary artery disease (CAD) risk loci, we explore pairwise statistical interactions between 8,068 SNPs from ten CAD genome-wide association studies (n=30,180). We discovered rs1800769 and rs9458001 in the vicinity of the LPA locus to interact in modulating CAD risk (P=1.75×10−13). Specific genotypes (e.g., rs1800769 CT) displayed either significantly decreased or increased risk for CAD in the context of genotypes of the respective other SNP (e.g., rs9458001 GG vs. AA). In the UK Biobank (n=450,112) significant interaction of this SNP pair was replicated for CAD (P=3.09×10−22), and was also found for aortic valve stenosis (P=6.95×10−7) and peripheral arterial disease (P=2.32×10−4). Identical interaction patterns affected circulating lipoprotein(a) (n=5,953; P=8.7×10−32) and hepatic apolipoprotein(a) (apo(a)) expression (n=522, P=2.6×10−11). We further interrogated potential biological implications of the variants and propose a mechanism explaining epistasis that ultimately may translate to substantial cardiovascular risks.
Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline
Authors: Overacker Ross D. , Banerjee Somdev , Neuhaus George F. , Sephton Selena Milicevic , Herrmann Alexander , Strother James A. , Brack-Werner Ruth , Blakemore Paul R. , Loesgen Sandra
Published: January 2019

Inspired by bioactive biaryl-containing natural products found in plants and the marine environment, a series of synthetic compounds belonging to the azaBINOL chiral ligand family was evaluated for antiviral activity against HIV-1. Testing of 39 unique azaBINOLs in a singleround infectivity assay resulted in the identification of three promising antiviral compounds, including 7-isopropoxy-8-(naphth-1-yl)quinoline (azaBINOLB#24), which exhibited low-micromolar activity. The active compounds and several close structural analogues were further tested against three different HIV-1 envelope pseudotyped viruses as well as in a full-virus replication system (EASY-HIT). Mode-of-action studies using a time-of-addition assay indicated that azaBINOLB#24acts after viral entry but before viral assembly and budding. HIV-1 reverse transcriptase (RT) assays that individually test for polymerase and RNase H activity were used to demonstrate thatB#24inhibits RNase H activity, most likely allosterically. Further binding analysis using bio-layer interferometry (BLI) showed thatB#24interacts with HIV-1 RT in a highly specific manner. These results indicate that azaBINOLB#24is a potentially viable, novel lead for the development of new HIV-1 RNase H inhibitors. Furthermore, this study demonstrates that the survey of libraries of synthetic compounds, designed purely with the goal of facilitating chemical synthesis in mind, may yield unexpected and selective drug leads for the development of new antiviral agents.
The genomes of polyextremophilic Cyanidiales contain 1% horizontally transferred genes with diverse adaptive functions
Authors: Rossoni Alessandro W. , Price Dana C. , Seger Mark , Lyska Dagmar , Lammers Peter , Bhattacharya Debashish , Weber Andreas P.M.
Published: January 2019

The role and extent of horizontal gene transfer (HGT) in eukaryotes are hotly disputed topics that impact our understanding regarding the origin of metabolic processes and the role of organelles in cellular evolution. We addressed this issue by analyzing 10 novel Cyanidiales genomes and determined that 1% of their gene inventory is HGT-derived. Numerous HGT candidates originated from polyextremophilic prokaryotes that live in similar habitats as the Cyanidiales and encodes functions related to polyextremophily. HGT candidates differ from native genes in GC-content, number of splice sites, and gene expression. HGT candidates are more prone to loss, which may explain the nonexistence of a eukaryotic pan-genome. Therefore, absence of a pan-genome and cumulative effects fail to provide substantive arguments against our hypothesis of recurring HGT followed by differential loss in eukaryotes. The maintenance of 1% HGTs, even under selection for genome reduction underlines the importance of non-endosymbiosis related foreign gene acquisition.
Absolute and relative pitch processing in the human brain: Neural and behavioral evidence
Authors: Leipold Simon , Brauchli Christian , Greber Marielle , Jäncke Lutz
Published: January 2019

Pitch is a primary perceptual dimension of sounds and is crucial in music and speech perception. When listening to melodies, most humans encode the relations between pitches into memory using an ability called relative pitch (RP). A small subpopulation, almost exclusively musicians, preferentially encode pitches using absolute pitch (AP): the ability to identify the pitch of a sound without an external reference. In this study, we recruited a large sample of musicians with AP (AP musicians) and without AP (RP musicians). The participants performed a pitch-processing task with a Listening and a Labeling condition during functional magnetic resonance imaging. General linear model analysis revealed that while labeling tones, AP musicians showed lower blood oxygenation level dependent (BOLD) signal in the inferior frontal gyrus and the presupplementary motor area — brain regions associated with working memory, language functions, and auditory imagery. At the same time, AP musicians labeled tones more accurately suggesting that AP might be an example of neural efficiency. In addition, using multivariate pattern analysis, we found that BOLD signal patterns in the inferior frontal gyrus and the presupplementary motor area differentiated between the groups. These clusters were similar, but not identical compared to the general linear model-based clusters. Therefore, information about AP and RP might be present on different spatial scales. While listening to tones, AP musicians showed increased BOLD signal in the right planum temporale which may reflect the matching of pitch information with internal templates and corroborates the importance of the planum temporale in AP processing.
Brain activity links performance in science reasoning with conceptual approach
Authors: Bartley Jessica E. , Riedel Michael C. , Salo Taylor , Boeving Emily R. , Bottenhorn Katherine L. , Bravo Elsa I. , Odean Rosalie , Nazareth Alina , Laird Robert W. , Sutherland Matthew T. , Pruden Shannon M. , Brewe Eric , Laird Angela R.
Published: January 2019

Understanding how students learn is crucial for helping them succeed. We examined brain function in 107 undergraduate students during a task known to be challenging for many students – physics problem solving – to characterize underlying neural mechanisms and determine how these support comprehension and proficiency. Further, we applied module analysis to response distributions, defining groups of students who answered using similar physics conceptions, and probed for brain differences linked with different conceptual approaches. We found integrated executive, attentional, visual motion, and default mode brain systems cooperate to achieve sequential and sustained physics-related cognition. While accuracy alone did not predict brain function, dissociable brain patterns were observed when students solved problems using different physics conceptions, and increased success was linked to conceptual coherence. Our analyses demonstrate that episodic associations and control processes operate in tandem to support physics reasoning, offering insight into effective classroom practices to promote student success.
Characterization of Cas proteins for CRISPR-Cas editing in streptomycetes
Authors: Yeo Wan Lin , Heng Elena , Tan Lee Ling , Lim Yi Wee , Lim Yee Hwee , Hoon Shawn , Zhao Huimin , Zhang Mingzi M , Wong Fong T.
Published: January 2019

Application of the well-characterized Streptococcus pyogenes CRISPR-Cas9 system in actinomycetes has enabled high efficiency multiplex genome editing and CRISPRi-mediated transcriptional regulation in these prolific bioactive metabolite producers. Nonetheless, SpCas9 has its limitations and can be ineffective depending on the strains and target sites. Here, we built and tested alternative CRISPR-Cas constructs based on the standalone pCRISPomyces-2 editing plasmid. We showed that Streptococcus thermophilus CRISPR1 (sth1Cas9), Staphylococcus aureus Cas9 (saCas9), and Francisella tularensis subsp. Novicida U112 Cpf1 (fnCpf1) are functional in multiple streptomycetes enabling efficient homology directed repair (HDR)-mediated knock-in and deletion. In strains where spCas9 was non-functional, these alternative Cas systems enabled precise genomic modifications within biosynthetic gene clusters for the discovery, production and diversification of natural products. These additional Cas proteins provide us with the versatility to overcome the limitations of individual CRISPR-Cas systems for genome editing and transcriptional regulation of these industrially important bacteria.
Selection and Biodiversity change
Authors: Godsoe William , Eisen Katherine E. , Stanton Daniel , Sirianni Katherine M
Published: January 2019

There is a great need to understand how and why biodiversity, which we define as the variety of organisms found in a given place, changes over time. Current estimates suggest strikingly slow change in traditional measures of biodiversity. These estimates seem to contradict rapid shifts in the abundance of individual species and have led to a rethinking of the mechanisms shaping biodiversity. Conceptual models emphasize the role of competition among species or, more recently, selection on species identity (i.e. selection that favors some species at the expense of others). However, it is difficult to quantify how these mechanisms contribute to biodiversity change. To illustrate this point we present cases where strong competition or selection on species identity leads to no biodiversity change. In view of this disconnect we develop a new approach to studying biodiversity change using the Price equation. We show that biodiversity change responds to selection on species’ rarity, rather than to either competition or selection on species identity. We then show how this insight can be used to quantify the effects of the mechanisms previously thought to influence biodiversity: 1) selection, 2) (ecological) drift, 3) immigration and 4) speciation. Our results suggest the connection between species’ fates and their rarity is fundamental to understanding biodiversity change.
Thyroid hormone regulates distinct paths to maturation in pigment cell lineages
Authors: Saunders Lauren , Mishra Abhishek , Aman Andrew J , Lewis Victor , Toomey Matthew B , Packer Jonathan , McFaline-Figueroa Jose , Qiu Xiaojie , Corbo Joseph C , Trapnell Cole , Parichy David M
Published: January 2019

Circulating endocrine factors are critical for orchestrating complex developmental processes during the generation of adult form. One such factor, thyroid hormone, regulates diverse cellular processes during post-embryonic development and can drive disparate morphological outcomes through mechanisms that remain essentially unknown. We sought to define how thyroid hormone elicits opposite responses in the abundance of two pigment cell classes during development of the zebrafish adult pigment pattern. By profiling individual transcriptomes from thousands of neural crest derived cells, including pigment cells, we reconstructed developmental trajectories and identified lineage-specific changes in response to thyroid hormone. Our findings show that thyroid hormone and its receptors regulate distinct events of cellular maturation across lineages, and illustrate how a single, global factor integrates seemingly divergent morphogenetic outcomes across developmental time.
Integration of Mouse and Human Single-cell RNA Sequencing Infers Spatial Cell-type Composition in Human Brains
Authors: Johnson Travis S , Abrams Zachary B , Helm Bryan R , Neidecker Peter , Machiraju Raghu , Zhang Yan , Huang Kun , Zhang Jie
Published: January 2019

Technical advances have enabled the identification of high-resolution cell types within tissues based on single-cell transcriptomics. However, such analyses are restricted in human brain tissue due to the limited number of brain donors. In this study, we integrate mouse and human data to predict cell-type proportions in human brain tissue, and spatially map the resulting cellular composition. By applying feature selection and linear modeling, combinations of human and mouse brain single-cell transcriptomics profiles can be integrated to "fill in" missing information. These combined "in silico chimeric" datasets are used to model the composition of nine cell types in 3,702 human brain samples in six Allen Human Brain Atlas (AHBA) donors. Cell types were spatially consistent regardless of the scRNA-Seq dataset (91% significantly correlated) or AHBA donor (p-value = 4.43E-20 by t-test) used in the model. Importantly, neuron nuclei location and neuron mRNA location were correlated only after accounting for neural connectivity (p-value = 1.26E-10), which supports the notion that gene expression is a better indicator than nuclei location of cellular localization for cells with large and irregularly shaped cell bodies, such as neurons. These results advocate for the integration of mouse and human data in models of brain tissue heterogeneity.
Optimal sparse olfactory representations persist in a plastic network
Authors: Assisi Collins , Stopfer Mark , Bazhenov Maxim
Published: January 2019

The neural representation of a stimulus is repeatedly transformed as it moves from the sensory periphery to deeper layers of the nervous system. Sparsening transformations are thought to increase the separation between similar representations, encode stimuli with great specificity, maximize storage capacity as associative memories, and provide an energy efficient instantiation of information in neural circuits. In the insect olfactory system, odors are initially represented in the periphery as a combinatorial code with simple temporal dynamics. Subsequently, in the antennal lobe this representation is transformed into a dense spatiotemporal activity pattern. Next, in the mushroom body Kenyon cells (KCs), the representation is dramatically sparsened. Then in mushroom body output neurons (MBONs), the representation takes on a new dense spatiotemporal format. Here, we develop a computational model to simulate this chain of olfactory processing from the receptor neurons to MBONs. We demonstrate that representations of similar odorants are maximally separated, measured by the distance between the corresponding MBON activity vectors, when KC responses are sparse and that the sparseness is maintained across variations in odor concentration by adjusting the feedback inhibition KCs receive. Different odor concentrations require different strength and timing of feedback inhibition for optimal processing. Further, in vivo, the KC–MBON synapse is highly plastic, and changes in synaptic strength after learning can change the balance of excitation and inhibition and may lead to a change in the distance between MBON activity vectors of two odorants for the same level of KC population sparseness. Thus, what is an optimal degree of sparseness before odor learning, could be rendered sub–optimal post learning. Here, we show, however, that synaptic weight changes caused by spike timing dependent plasticity increase the distance between the odor representations from the perspective of MBONs and do not lead to a concomitant change in the optimal sparseness.

Author Summary

Kenyon cells (KCs) of the mushroom body represent odors as a sparse code. When viewed from the perspective of follower neurons, mushroom body output neurons (MBONs), an optimal level of KC sparseness maximally separates the representations of odors. However, the KC–MBON synapse is highly plastic and may be potentiated or depressed by odor–driven experience that could, in turn, perturb the optimality formed by pre–synaptic circuits. Contrary to this expectation, we show that synaptic plasticity based on spike timing of pre- and postsynaptic neurons improves the ability of the system to distinguish between the representations of similar odors while preserving the optimality determined by pre–synaptic circuits.
N6-methyladenosine dynamics during early vertebrate embryogenesis
Authors: Aanes Håvard , Engelsen Dominique , Manaf Adeel , Alemu Endalkachew Ashenafi , Vågbø Cathrine Broberg , Martín Leonardo , Lerdrup Mads , Hansen Klaus , Mathavan Sinnakaruppan , Winata Cecilia , Darnell Robert B. , Aleström Peter , Klungland Arne
Published: January 2019

Early vertebrate embryogenesis is characterized by extensive post-transcriptional regulation during the maternal-to-zygotic transition. The N6-methyladenosine (m6A) modifications on mRNA have been shown to affect both translation and stability of transcripts. Here we investigate the m6A topology during early vertebrate embryogenesis and its association with polyadenylated mRNA levels. The majority (>70%) of maternal transcripts harbor m6A, and there is a substantial increase of m6A in the polyadenylated mRNA fraction between 0 and 2 hours post fertilization. Notably, we find strong associations between m6A, cytoplasmic polyadenylation and translational efficiency prior to zygotic genome activation (ZGA). Interestingly, the relationship between m6A and translation is strongest for peaks located in the 3’UTR, but not overlapping stop codons. Sequence analyses revealed enrichment of motifs for RNA binding proteins involved in translational regulation and RNA degradation. After ZGA, m6A seem to diminish the effect of miR-430 mediated degradation. The reported results improve our understanding of the combinatorial code behind post-transcriptional mRNA regulation during embryonic reprogramming and early differentiation.
Life history parameters in acellular extrinsic fiber cementum microstructure
Authors: Edinborough Marija , Fearn Sarah , Pilgrim Matthew , Cvetković Andrijana , Mihailović Branko , Grbić Rade , Edinborough Kevan
Published: January 2019

Life-history parameters such as pregnancies, skeletal trauma, and renal disease have previously been identified from hypomineralized growth layers (incremental lines) of acellular extrinsic fiber cementum (AEFC). The precise periodicity of these growth layers remains vaguely approximated, so causal life-history explanations using tooth cementum cannot yet be rigorously calculated or tested. On the other hand, we show how life history parameters in AEFC can be identified by two contrasting elemental detection methods. Based on our results we reject the possibility of accurate estimation of pregnancies and other life history parameters from cementum using scanning electron microscopy alone. Here, we propose a new methodological approach for cementum research, Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), to measure degree and distribution of mineralization of cementum growth layers. Our results show that Tof-SIMS can significantly increase our knowledge of cementum composition and is therefore a powerful new tool for life history researchers.
Homochiral and racemic MicroED structures of a peptide repeat from the ice-nucleation protein InaZ
Authors: Zee Chih-Te , Glynn Calina , Gallagher-Jones Marcus , Miao Jennifer , Santiago Carlos G. , Cascio Duilio , Gonen Tamir , Sawaya Michael R. , Rodriguez Jose A.
Published: January 2019

The ice-nucleation protein InaZ from Pseudomonas syringae contains a large number of degenerate repeats that span more than a quarter of its sequence and include the segment GSTSTA. Ab initio structures of this repeat segment, resolved to 1.1 Å by microfocus X-ray crystallography and to 0.9 Å by the cryo-EM method MicroED, were determined from both racemic and homochiral crystals. The benefits of racemic protein crystals for structure determination by MicroED were evaluated and it was confirmed that the phase restriction introduced by crystal centrosymmetry increases the number of successful trials during the ab initio phasing of the electron diffraction data. Both homochiral and racemic GSTSTA form amyloid-like protofibrils with labile, corrugated antiparallel β-sheets that mate face to back. The racemic GSTSTA protofibril represents a new class of amyloid assembly in which all-left-handed sheets mate with their all-right-handed counterparts. This determination of racemic amyloid assemblies by MicroED reveals complex amyloid architectures and illustrates the racemic advantage in macromolecular crystallography, now with submicrometre-sized crystals.
A cytosine modification mechanism revealed by the structure of a ternary complex of deoxycytidylate hydroxymethylase from bacteriophage T4 with its cofactor and substrate
Authors: Park Si Hoon , Suh Se Won , Song Hyun Kyu
Published: January 2019

To protect viral DNA against the host bacterial restriction system, bacteriophages utilize a special modification system – hydroxymethylation – in which dCMP hydroxymethylase (dCH) converts dCMP to 5-hydroxymethyl-dCMP (5hm-dCMP) usingN5,N10-methylenetetrahydrofolate as a cofactor. Despite shared similarity with thymidylate synthase (TS), dCH catalyzes hydroxylation through an exocyclic methylene intermediate during the last step, which is different from the hydride transfer that occurs with TS. In contrast to the extensively studied TS, the hydroxymethylation mechanism of a cytosine base is not well understood due to the lack of a ternary complex structure of dCH in the presence of both its substrate and cofactor. This paper reports the crystal structure of the ternary complex of dCH from bacteriophage T4 (T4dCH) with dCMP and tetrahydrofolate at 1.9 Å resolution. The authors found key residues of T4dCH for accommodating the cofactor without a C-terminal tail, an optimized network of ordered water molecules and a hydrophobic gating mechanism for cofactor regulation. In combination with biochemical data on structure-based mutants, key residues within T4dCH and a substrate water molecule for hydroxymethylation were identified. Based on these results, a complete enzyme mechanism of dCH and signature residues that can identify dCH enzymes within the TS family have been proposed. These findings provide a fundamental basis for understanding the pyrimidine modification system.
Synthesis, structure and selective luminescence sensing for iron(III) ions of a three-dimensional zinc(II) (4,6)-connected coordination network
Authors: Su Feng , Zhou Cheng-Yong , Wu Lin-Tao , Wu Xi , Han Chun , Wang Zhi-Jun
Published: January 2019

Coordination polymers constructed from conjugated organic ligands and metal ions with a d
10 electronic configuration exhibit intriguing properties for chemical sensing and photochemistry. A ZnII-based coordination polymer, namely poly[aqua(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)(μ2-4,4′-bipyridine)dizinc(II)], [Zn2(C16H6O8)(C10H8N2)(H2O)2]
n
or [Zn2(m,m-bpta)(4,4′-bipy)(H2O)2]
n
, was synthesized from a mixture of biphenyl-3,3′,5,5′-tetracarboxylic acid [H4(m,m-bpta)], 4,4′-bipyridine (4,4′-bipy) and Zn(NO3)2·6H2O under solvothermal conditions. The title complex has been structurally characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction and powder X-ray diffraction analysis, and features a μ6-coordination mode. The ZnII ions adopt square-pyramidal geometries and are bridged by two syn–syn carboxylate groups to form [Zn2(COO)2] secondary buildding units (SBUs). The SBUs are crosslinked by (m,m-bpta)4− ligands to produce a two-dimensional grid-like layer that exhibits a stair-like structure along the a axis. Adjacent layers are linked by 4,4′-bipy ligands to form a three-dimensional network with a {44.610.8}{44.62} topology. In the solid state, the complex displays a strong photoluminescence and an excellent solvent stability. In addition, the luminescence sensing results indicate a highly selective and sensitive sensing for Fe3+ ions.
Crystal structure of the programmed cell death 5 protein from Sulfolobus solfataricus
Authors: Lin Kuan-Fu , Hsu Jia-Yuan , Hsieh Dong-Lin , Tsai Meng-Ju , Yeh Ching-Hui , Chen Chin-Yu
Published: January 2019

Programmed cell death 5 (PDCD5) is a vital signaling protein in the apoptosis pathway in eukaryotes. It is known that there are two dissociated N-terminal regions and a triple-helix core in eukaryotic PDCD5. Structural and functional studies of PDCD5 from hyperthermophilic archaea have been limited to date. Here, the PDCD5 homolog Sso0352 (SsoPDCD5) was identified in Sulfolobus solfataricus, the SsoPDCD5 protein was expressed and crystallized, and the phase was identified by single-wavelength anomalous diffraction. The native SsoPDCD5 crystal belonged to space group C2 and diffracted to 1.49 Å resolution. This is the first crystal structure of a PDCD5 homolog to be solved. SsoPDCD5 shares a similar triple-helix bundle with eukaryotic PDCD5 but has a long α-helix in the N-terminus. A structural search and biochemical data suggest that SsoPDCD5 may function as a DNA-binding protein.
Structure of an Influenza A virus N9 neuraminidase with a tetrabrachion-domain stalk
Authors: Streltsov Victor A. , Schmidt Peter M. , McKimm-Breschkin Jennifer L.
Published: January 2019

The influenza neuraminidase (NA) is a homotetramer with head, stalk, transmembrane and cytoplasmic regions. The structure of the NA head with a stalk has never been determined. The NA head from an N9 subtype influenza A virus, A/tern/Australia/G70C/1975 (H1N9), was expressed with an artificial stalk derived from the tetrabrachion (TB) tetramerization domain fromStaphylothermus marinus. The NA was successfully crystallized both with and without the TB stalk, and the structures were determined to 2.6 and 2.3 Å resolution, respectively. Comparisons of the two NAs with the native N9 NA structure from egg-grown virus showed that the artificial TB stalk maintained the native NA head structure, supporting previous biological observations.