bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative Nerve Blocks Fail to Improve Quality of Recovery after Tissue Expander Breast Reconstruction: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial
Authors: Lanier Steven T. , Lewis Kevin C. , Kendall Mark C. , Vieira Brittany L. , De Oliveira Gildasio , Nader Anthony , Kim John Y. S. , Alghoul Mohammed
Published: February 2018

Background:

The authors’ study represents the first level I evidence to assess whether intraoperative nerve blocks improve the quality of recovery from immediate tissue expander/implant breast reconstruction.

Methods:

A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in which patients undergoing immediate tissue expander/implant breast reconstruction were randomized to either (1) intraoperative intercostal and pectoral nerve blocks with 0.25% bupivacaine with 1:200,000 epinephrine and 4 mg of dexamethasone or (2) sham nerve blocks with normal saline. The 40-item Quality of Recovery score, pain score, and opioid use in the postoperative period were compared statistically between groups. Power analysis ensured 80 percent power to detect a 10-point (clinically significant) difference in the 40-item Quality of Recovery score.

Results:

Forty-seven patients were enrolled. Age, body mass index, laterality, mastectomy type, and lymph node dissection were similar between groups. There were no statistical differences in quality of recovery, pain burden as measured by visual analogue scale, opioid consumption, antiemetic use, or length of hospital stay between groups at 24 hours after surgery. Mean global 40-item Quality of Recovery scores were 169 (range, 155 to 182) for the treatment arm and 165 (range, 143 to 179) for the placebo arm (p = 0.36), indicating a high quality of recovery in both groups.

Conclusion:

Although intraoperative nerve blocks can be a safe adjunct to a comprehensive postsurgical recovery regimen, the authors’ results indicate no effect on overall quality of recovery from tissue expander/implant breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Where Do We Look? Assessing Gaze Patterns in Breast Reconstructive Surgery with Eye-Tracking Technology
Authors: Cai Lawrence Z. , Paro John A. M. , Lee Gordon K. , Nazerali Rahim S.
Published: February 2018

Background:

Aesthetics plays a large role in determining a successful outcome in plastic and reconstructive surgery. As such, understanding perceptions of favorable aesthetics is crucial for optimizing patient satisfaction. Eye-tracking technology offers an unbiased way of measuring how viewers evaluate breast reconstructions.

Methods:

Twenty-nine raters with varied plastic surgery experience were shown 20 images of breast reconstruction at various stages. Breasts were divided into those with nipples and no reconstruction scars, those with nipples and reconstruction scars, and those with reconstruction scars and no nipples. Raters viewed each image for 8 seconds to evaluate aesthetic outcomes. Eye-tracking equipment and software were used to track raters’ gaze and analyze the distribution of attention.

Results:

In breasts with reconstruction scars and no nipples, viewers spent 53.9 percent of the view time examining scars, whereas viewers’ attention was divided evenly in breasts with both reconstruction scars and nipples, spending 27.5 percent and 27.7 percent of view time examining the nipples and reconstruction scars, respectively. When examining complete reconstructions, viewers spent more time scanning the entire image before fixating on scars and spent less time on single-site fixation.

Conclusions:

Complete reconstructions, which notably include the final nipple-areola complex, appear to play an important role in restoring normal viewing parameters. In essence, completed breast reconstructions with nipple-areola complexes divert attention from extraneous surgical scars and lead viewers to assess the breasts more holistically. Eye-tracking technology provides a powerful link between objective gaze and viewer attention that may potentially be used to predict subjective aesthetic preferences.
Evaluation of Acellular Dermal Matrix Efficacy in Prosthesis-Based Breast Reconstruction
Authors: Sobti Nikhil , Ji Emily , Brown Rebecca L. , Cetrulo Curtis L. , Colwell Amy S. , Winograd Jonathan M. , Austen William G. , Liao Eric C.
Published: February 2018

Background:

Although many studies have examined the safety of acellular dermal matrix in immediate prosthetic breast reconstruction, few studies have evaluated efficacy. This study examined initial tissue expander fill volume as a marker of efficacy, comparing patients after staged prosthetic breast reconstruction assisted with acellular dermal matrix versus breast reconstruction not assisted with acellular dermal matrix. Number of fill visits and time interval to implant exchange were examined as secondary endpoints.

Methods:

An institutional review board–approved retrospective chart review was conducted to identify consecutive staged prosthetic reconstruction cases over 12 years.

Results:

Mean initial tissue expander fill volume was significantly higher in the acellular dermal matrix group compared with the non–acellular dermal matrix group (180.8 ± 150.0 versus 45.8 ± 74.4; p = 0.00). Normalizing for final implant size, the acellular dermal matrix group exhibited significantly higher perioperative fill (0.33 ± 0.24 versus 0.11 ± 0.16; p = 0.00). A collinear trend was observed between acellular dermal matrix use and direct-to-implant reconstruction procedures during the study period.

Conclusions:

These results suggest that acellular dermal matrix use is more efficacious in achieving greater initial fill volume, fewer visits for expansion, and a shorter time interval to implant exchange compared with non–acellular dermal matrix procedures. The authors also describe a collinear relationship between acellular dermal matrix use and transition to direct-to-implant procedures at their institution. This work serves as a framework for future studies evaluating acellular dermal matrix efficacy, and guides innovation of biomaterials to support breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
β-Catenin–Dependent Wnt Signaling: A Pathway in Acute Cutaneous Wounding [RETRACTED]
Authors: Carre Antoine L. , Hu Michael S. , James Aaron W. , Kawai Kenichiro , Galvez Michael G. , Longaker Michael T. , Lorenz H. Peter
Published: February 2018

Background:

Acute wound healing is a dynamic process that results in the formation of scar tissue. The mechanisms of this process are not well understood; numerous signaling pathways are thought to play a major role. Here, the authors have identified β-catenin–dependent Wnt signaling as an early acute-phase reactant in acute wound healing and scar formation.

Methods:

The authors created 6-mm full-thickness excisional cutaneous wounds on adult β-catenin–dependent Wnt signal (BAT-gal) reporter mice. The expression of canonical Wnt after wounding was analyzed using X-gal staining and quantitative real-time polymerase chain reaction. Next, recombinant mouse Wnt3a (rmWnt3a) was injected subcutaneously to the wound edge, daily. The mice were killed at stratified time points, up to 15 days after injury. Histologic analysis, quantitative real-time polymerase chain reaction, and Western blot were performed.

Results:

Numerous individual Wnt ligands increased in expression after wounding, including Wnt3a, Wnt4, Wnt10a, and Wnt11. A specific pattern of Wnt activity was observed, localized to the hair follicle and epidermis. Mice injected with rmWnt3a exhibited faster wound closure, increased scar size, and greater expression of fibroblast growth factor receptor-2 and type I collagen.

Conclusions:

The authors’ data suggest that β-catenin–dependent Wnt signaling expression increases shortly after cutaneous wounding, and exogenous rmWnt3a accelerates reepithelialization, wound matrix maturation, and scar formation. Future experiments will focus on the intersection of Wnt signaling and other known profibrotic cytokines.
68Ga-DOTANOC PET/CT in Medulloblastoma
Authors: Arunraj Sreedharan Thankarajan , Parida Girish Kumar , Damle Nishikant Avinash , Arora Saurabh , Reddy Sreenivasa , Chakraborty Dhritiman , Prabhu Meghna , Tripathi Madhavi , Bal Chandrasekhar
Published: February 2018

Medulloblastoma, also known as cerebellar primitive neuroectodermal tumor, is the most common brain tumor in children and arises in the posterior cranial fossa. We present the case of a patient with desmoplastic type of medulloblastoma, which showed recurrence more than once. When 68Ga-DOTANOC PET-CT was done, the lesions showed somatostatin receptor expression, opening another potential therapeutic option for this patient.
Atypical Appearance on Thyroid Scintigraphy
Authors: Arcay Ayca , Ozgur Ozhan , Aydin Funda
Published: February 2018

We report the case of a 49-year-old woman with achalasia in whom thyroid stimulating hormone supression was incidentally detected on routine blood tests and who therefore underwent thyroid scintigraphy. Thyroid scan demonstrated low intensity diffuse technetium 99mTc sodium pertechnetate accumulation inferior to thyroid gland. After correlating the images with her previous barium esophagogram, tracer accumulation caudal to thyroid gland was explained on the presumption of 99mTc sodium pertechnetate retention within the dilated esophagus.
FDG PET/CT of Chromophobe Renal Cell Carcinoma With Sarcomatoid Differentiation
Authors: Lee Chee H. , Kesari Vivek , Legesse Teklu , Chen Wengen
Published: February 2018

We report the case of a 49-year-old white man with a chromophobe renal cell carcinoma associated with sarcomatoid differentiation, an uncommon yet an aggressive form of dedifferentiated renal cell carcinoma. In opposite to the conventional renal cell carcinoma, which may not always demonstrate avid FDG activity, the sarcomatoid differentiated chromophobe renal cell carcinoma shows intense FDG uptake on PET. This case highlights the role of FDG PET/CT in staging and restaging this type of rare renal cell carcinoma.
Osteofascial Radial Forearm Free Flap Reconstruction of Midface Defect After Resection of Intraosseous Hemangioma
Authors: Johnson Jeffrey , Karni Ron , Ho Tang
Published: February 2018

Introduction:

Intraosseous hemangiomas of the midface are rare with few reported cases in the literature. Various reconstructive methods have been previously described, but none using vascularized bone graft secondary to the benign nature of the tumor and often relatively limited defect size.

Clinical Report:

The authors present the case of a 47-year-old man with a biopsy proven enlarging right maxillary intraosseous cavernous hemangioma which was resected primarily, resulting in a large defect involving the entire zygomaticomaxillary buttress and a portion of the right orbital floor and malar prominence. Given the structural involvement and the significant bony defect size, this was simultaneously reconstructed using an osteofascial radial forearm free flap and orbital floor titanium implant with satisfactory outcome.
The Guiding Lateral Z Osteotomy for the Correction of Vertical Orbital Dystopia
Authors: Kohno Hikaru , Sakamoto Yoshiaki , Miwa Tomoru , Yoshida Kazunari , Kishi Kazuo
Published: February 2018

Transcranial vertical orbital translocation is useful for correcting vertical orbital dysplasia. However, the technique is limited by the degree of uncertainty regarding the amount of vertical movement required after the osteotomy. As for landmark movement, Z osteotomy is performed as part of a box osteotomy. This technique is useful in that it is easy to know how far the orbit should be moved, and stabilization can be obtained.
Craniovertebral Junction Abnormalities in Surgical Patients With Congenital Muscular Torticollis
Authors: Ahn Ah-Reum , Rah Ueon Woo , Woo Ji-Eun , Park Sunghoon , Kim Sanghyun , Yim Shin-Young
Published: February 2018

Our clinical experience led us to realize that craniovertebral junction (CVJ) abnormalities were common in surgical patients with congenital muscular torticollis (CMT). This study aimed to report the concurrence rate of CVJ abnormalities in surgical patients with CMT, along with comprehensive evaluation of type of concurrent CVJ abnormalities. This was a retrospective cohort study in a tertiary hospital, including 41 subjects who underwent surgical release for CMT at the mean age of 8.38 years. The presence of CVJ abnormalities was analyzed, using craniofacial 3-dimensional computed tomography images. The concurrence rate of CVJ abnormalities was 70% in surgical patients with CMT. Subjects with CVJ abnormalities had, on average, 1.48 abnormalities. The CVJ abnormalities were rotation and lateral shift of the atlanto-axial joint along with rotation of atlanto-occipital joint, where rotation of the atlanto-axial joint was most common (82.76%). There is no patient with anterior shift of the atlanto-axial joint. Chronic mechanical tension by the contracted unilateral sternocleidomastoid muscle of CMT could be responsible for concurrent CVJ abnormalities. The CVJ abnormalities are more common in the atlanto-axial joint than in the atlanto-occipital joint. In conclusions, CVJ abnormality seems to be a common concurrent skeletal complication of CMT, at least, in surgical patients. The CVJ abnormality might be included in the list of skeletal complications of CMT. If CVJ abnormalities are significantly more common in surgical patients with CMT, CVJ abnormalities might be one of predictors of surgical patients with CMT.
Is Coincidental Rhinosinusitis a Predisposing Factor for Postoperative Central Nervous System Infection After Endoscopic Endonasal Transsphenoidal Surgery?
Authors: Kim Do Hyun , Hong Yong-Kil , Jeun Sin-Soo , Park Jae-Sung , Kim Soo Whan , Cho Jin Hee , Park Yong Jin , Kim Junghwan , Park Moon Il , Kim Sung Won
Published: February 2018

Background:

To investigate the effect of rhinosinusitis in patients who undergo surgery via the endoscopic endonasal transsphenoidal approach (EETSA).

Methods:

The authors retrospectively reviewed the medical records of patients who underwent surgery via the EETSA between February 2009 and November 2016. In total, 505 patients were included in the study. Preoperative paranasal sinus computed tomography, sellar magnetic resonance imaging, and nasal endoscopy were performed for all the patients.

Results:

Fifteen patients without sphenoid sinusitis underwent surgery with the concomitant transsphenoidal approach and functional endoscopic sinus surgery, and showed no central nervous system (CNS) complication. During surgery via the EETSA, the presence of rhinosinusitis did not significantly affect the incidence of postoperative CNS infection (P = 0.051), except for sphenoid sinusitis (P = 0.003). Conversely, the incidence of postoperative CNS infection was not related significantly to the Lund–Mackay score or tumor size. The risk of CNS infection was 12.151-fold higher in patients with sphenoid sinusitis (95% confidence interval, 3.153–46.827; P ≤ 0.001).

Conclusion:

Surgery via the EETSA and functional endoscopic sinus surgery can be safely performed together in most patients with rhinosinusitis. However, sphenoid sinus infection appears to be a predisposing factor for postoperative CNS infection. Therefore, a separate surgical procedure for sphenoid lesions should be considered in these patients before the use of the EETSA.
Optimal timing of initial debridement for necrotizing soft tissue infection: A Practice Management Guideline from the Eastern Association for the Surgery of Trauma
Authors: Gelbard Rondi B. , Ferrada Paula , Yeh D. Dante , Williams Brian H. , Loor Michele , Yon James , Mentzer Caleb , Khwaja Kosar , Khan Mansoor A. , Kohli Anirudh , Bulger Eileen M. , Robinson Bryce R.H.
Published: February 2018

BACKGROUND

Necrotizing soft tissue infections (NSTI) are rare, life-threatening, soft-tissue infections characterized by rapidly spreading inflammation and necrosis of the skin, subcutaneous fat, and fascia. While it is widely accepted that delay in surgical debridement contributes to increased mortality, there are currently no practice management guidelines regarding the optimal timing of surgical management of this condition. Although debridement within 24 hours of diagnosis is generally recommended, the time ranges from 3 hours to 36 hours in the existing literature. Therefore, the objective of this article is to provide evidence-based recommendations for the optimal timing of surgical management of NSTI.

METHODS

The MEDLINE database using PubMed was searched to identify English language articles published from January 1990 to September 2015 regarding adult and pediatric patients with NSTIs. A systematic review of the literature was performed, and the Grading of Recommendations Assessment, Development and Evaluation framework were used. A single population [P], intervention [I], comparator [C], and outcome [O] (PICO) question was applied: In patients with NSTI (P), should early (<12 hours) initial debridement (I) versus late (≥12 hours) initial debridement (C) be performed to decrease mortality (O)?

RESULTS

Two hundred eighty-seven articles were identified. Of these, 42 papers underwent full text review and 6 were selected for guideline construction. A total of 341 patients underwent debridement for NSTI. Of these, 143 patients were managed with early versus 198 with late operative debridement. Across all studies, there was an overall mortality rate of 14% in the early group versus 25.8% in the late group.

CONCLUSION

For NSTIs, we recommend early operative debridement within 12 hours of suspected diagnosis. Institutional and regional systems should be optimized to facilitate prompt surgical evaluation and debridement.

LEVEL OF EVIDENCE

Systematic review/meta-analysis, level IV.
Injury in the transgender population: What the trauma surgeon needs to know
Authors: Morrison Shane D. , Kolnik Sarah M. , Massie Jonathan P. , Crowe Christopher S. , Dugi Daniel , Friedrich Jeffrey B. , Pham Tam N. , Berli Jens U. , O’Keefe Grant E. , Bulger Eileen M. , Maier Ronald V. , Mandell Samuel P.
Published: February 2018

Gender dysphoria, or the distress caused by the incongruence between a person’s assigned and experienced gender, can lead to significant psychosocial sequelae and increased risk of suicide (>40% of this population) and assault (>60% of this population). With an estimated 25 million transgender individuals worldwide and increased access to care for the transgender population, trauma surgeons are more likely to care for patients who completed or are in the process of medical gender transition. As transgender health is rarely taught in medical education, knowledge of the unique health care needs and possible alterations in anatomy is critical to appropriately and optimally treat transgender trauma victims. Considerations of cross-gender hormones and alterations of the craniofacial, laryngeal, chest, and genital systems are offered in this review. Further research on the optimal treatment mechanisms for transgender patients is needed.
Opinion on monoaminergic contributions to traits and temperament
Authors: Robbins T. W.
Published: February 2018

This article critically reviews evidence relating temperamental traits and personality factors to the monoamine neurotransmitters, especially dopamine and serotonin. The genetic evidence is not yet considered to be conclusive and it is argued that basic neuroscience research on the neural basis of behaviour in experimental animals should be taken more into account. While questionnaire and lexical methodology including the ‘Five Factor’ theory has been informative (mostly for the traits relevant to social functioning, i.e. personality), biologically oriented approaches should be employed with more objective, theoretically grounded measures of cognition and behaviour, combined with neuroimaging and psychopharmacology, where appropriate. This strategy will enable specific functions of monoamines and other neuromodulators such as acetylcholine and neuropeptides (such as orexin) to be defined with respect to their roles in modulating activity in specific neural networks—leading to a more realistic definition of their interactive roles in complex, biologically based traits (i.e. temperament).

This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences’.
Traits of empathy and anger: implications for psychopathy and other disorders associated with aggression
Authors: Blair R. J. R.
Published: February 2018

Empathy and anger are two social emotions that modulate an individual's risk for aggression. Empathy is an emotional reaction to another individual's emotional state. Anger is an emotional reaction to threat, frustration or social provocation. Reduced empathy, seen in psychopathy, increases the risk for goal-directed aggression. Atypically increased anger (i.e. irritability), seen in conditions like disruptive mood dysregulation disorder and borderline personality disorder, increases the risk for reactive aggression. In this paper, I will outline core neurocognitive functions that correspond to empathy and which are compromised in individuals with psychopathic traits. In addition, I will outline neurocognitive functions involved in either the generation or regulation of anger and which are compromised in psychiatric conditions at increased risk for irritability/reactive aggression. It can be hoped that improved understanding of empathy and anger will lead to better assessment tools and improved interventions to reduce aggression risk.

This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences’.
What is the natural measurement unit of temperament: single traits or profiles?
Authors: Cloninger C. Robert , Zwir Igor
Published: February 2018

There is fundamental doubt about whether the natural unit of measurement for temperament and personality corresponds to single traits or to multi-trait profiles that describe the functioning of a whole person. Biogenetic researchers of temperament usually assume they need to focus on individual traits that differbetweenindividuals. Recent research indicates that a shift of emphasis to understand processeswithinthe individual is crucial for identifying the natural building blocks of temperament. Evolution and development operate on adaptation of whole organisms or persons, not on individual traits or categories. Adaptive functioning generally depends on feedback among many variable processes in ways that are characteristic of complex adaptive systems, not machines with separate parts. Advanced methods of unsupervised machine learning can now be applied to genome-wide association studies and brain imaging in order to uncover the genotypic–phenotypic architecture of traits like temperament, which are strongly influenced by complex interactions, such as genetic epistasis, pleiotropy and gene–environment interactions. We have found that the heritability of temperament can be nearly fully explained by a large number of genetic variants that are unique for multi-trait profiles, not single traits. The implications of this finding for research design and precision medicine are discussed.

This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
Functionality versus dimensionality in psychological taxonomies, and a puzzle of emotional valence
Authors: Trofimova Irina
Published: February 2018

This paper applies evolutionary and functional constructivism approaches to the discussion of psychological taxonomies, as implemented in the neurochemical model Functional Ensemble of Temperament (FET). FET asserts that neurochemical systems developed in evolution to regulate functional-dynamical aspects of construction of actions: orientation, selection (integration), energetic maintenance, and management of automatic behavioural elements. As an example, the paper reviews the neurochemical mechanisms of interlocking between emotional dispositions and performance capacities. Research shows that there are no specific neurophysiological systems of positive or negative affect, and that emotional valence is rather an integrative product of many brain systems during estimations of needs and the capacities required to satisfy these needs. The interlocking between emotional valence and functional aspects of performance appears to be only partial since all monoamine and opioid receptor systems play important roles in non-emotional aspects of behaviour, in addition to emotionality. This suggests that the Positive/Negative Affect framework for DSM/ICD classifications of mental disorders oversimplifies the structure of non-emotionality symptoms of these disorders. Contingent dynamical relationships between neurochemical systems cannot be represented by linear statistical models searching for independent dimensions (such as factor analysis); nevertheless, these relationships should be reflected in psychological and psychiatric taxonomies.

This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences’.
Diversity in action: exchange of perspectives and reflections on taxonomies of individual differences
Authors: Uher Jana , Trofimova Irina , Sulis William , Netter Petra , Pessoa Luiz , Posner Michael I. , Rothbart Mary K. , Rusalov Vladimir , Peterson Isaac T. , Schmidt Louis A.
Published: February 2018

Throughout the last 2500 years, the classification of individual differences in healthy people and their extreme expressions in mental disorders has remained one of the most difficult challenges in science that affects our ability to explore individuals' functioning, underlying psychobiological processes and pathways of development. To facilitate analyses of the principles required for studying individual differences, this theme issue brought together prominent scholars from diverse backgrounds of which many bring unique combinations of cross-disciplinary experiences and perspectives that help establish connections and promote exchange across disciplines. This final paper presents brief commentaries of some of our authors and further scholars exchanging perspectives and reflecting on the contributions of this theme issue.

This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences’.
Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae
Authors: Wang Yonglin , Hu Xiaoping , Fang Yulin , Anchieta Amy , Goldman Polly H. , Hernandez Gustavo , Klosterman Steven J.
Published: February 2018

Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.
Sex specific endophenotypes of in-utero cannabinoid exposure
Authors: Bara Anissa , Manduca Antonia , Bernabeu Axel , Borsoï Milene , Servado Michela , Lassalle Olivier , Murphy Michelle N. , Wager-Miller Jim , Mackie Ken , Pelissier-Alicot Anne-Laure , Trezza Viviana , Manzoni Olivier J.
Published: February 2018

Cannabinoids can cross the placenta, thus may interfere with fetal endocannabinoid signaling during neurodevelopment, causing long-lasting deficits. Despite increasing cannabis consumption during pregnancy, the protracted consequences of prenatal cannabinoid exposure (PCE) remain incompletely understood. Here we report sex-specific differences in behavioral and neuronal deficits in the adult progeny of rat dams exposed to low doses of cannabinoids during gestation. In males, PCE reduced social interaction, ablated endocannabinoid long-term depression (LTD) and heightened excitability of prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and endocannabinoid signaling regulate emotional behavior and synaptic plasticity. Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of anandamide levels restored LTD and social interaction in PCE adult males. Together, these results highlight marked sexual differences in the effects of PCE and introduce strategies for reversing detrimental effects of PCE.
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx
Authors: Broertjes Jorrit , Klarenbeek Jeffrey , Habani Yasmin , Langeslag Michiel , Jalink Kees
Published: February 2018

The nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cAMP. Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.
The dynamic tumor ecosystem: how cell turnover and trade-offs affect cancer evolution
Authors: Gallaher Jill A. , Brown Joel , Anderson Alexander R. A.
Published: February 2018

ABSTRACT

Tumors are not static masses of cells but rather dynamic ecosystems where cancer cells experience constant turnover and evolve fitness-enhancing phenotypes. Selection for different phenotypes may vary with 1) the tumor niche (edge or core), 2) cell turnover rates, 3) the nature of the tradeoff between traits (proliferation vs migration), and 4) whether deaths occur in response to demographic or environmental stochasticity. In an agent based, spatially-explicit model, we observe how two traits (proliferation rate and migration speed) evolve under different trade-off conditions with different turnover rates. Migration rate is favored over proliferation at the tumor’s edge and vice-versa for the interior. Increasing cell turnover rates only slightly slows the growth of the tumor, but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration. A convex tradeoff tends to favor proliferation over migration while often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff slows the rate of evolution, and favors migration at low death rates and proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation at the expense of migration; and vice-versa for environmental stochasticity. All of these factors and their interactions contribute to the ecology of the tumor, tumor heterogeneity, trait evolution, and phenotypic variation. While diverse, these effects may be predictable and empirically accessible.
Insulation of gene expression by CTCF and cohesin-based subTAD (ubiquitous intra-TAD) loop structures in mouse liver
Authors: Matthews Bryan J. , Waxman David J.
Published: February 2018

CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present a computational method to identify cohesin-and-CTCF binding sites that form intra-TAD DNA loops (subTADs). We show that predicted subTAD anchors are structurally indistinguishable from those of TADs regarding their binding partners, sequence conservation, and resistance to cohesin knockdown; further, the subTAD loops retain key functional features of TADs, including insulation of chromatin contacts, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that subTADs form by the same loop extrusion mechanism as larger loops, and that their shorter length enables finer regulatory control over gene expression. 4C-seq analysis using an Alb promoter viewpoint illustrates the role of subTADs in restricting enhancer-promoter interactions. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization, and demonstrate that distal enhancer insulation by subTADs is widespread.
Distinct impacts of air and root-zone temperatures on leaf and root features of cucumber seedlings: resource acquisition capacity, organ size and carbon-nitrogen balance
Authors: Wang Xiaozhuo , Gao Lihong , Tian Yongqiang
Published: February 2018

Both low air (Tair) and root-zone (Troot) temperatures can inhibit resource (e.g. carbon and nutrients) acquisition by leaves and roots through various aspects, such as morphology, biomass allocation and assimilation/absorption capacity. However, it is still ambiguous whetherTairandTrootinfluence carbon (C) and nutrient acquisition via the same approach. To this end, in this study, cucumber (Cucumis sativusL.) seedlings were hydroponically grown under treatments arranged in complete factorial combination of two levels ofTair(26/18°C and 20/12°C, day/night) and two levels ofTroot(19°C and 13°C, constant). In general, bothTairandTrootaffected leaf and root sizes mainly by regulating their morphology rather than biomass investment. Under lowTairconditions (20/18°C), elevatedTroot(compare 19°C versus 13°C) did not influence C acquisition, but increased nitrogen (N) acquisition mainly due to an increase in relative root length, resulting in decreased C : N acquisition ratio. However, under lowTrootconditions (13°C), elevatedTair(compare 26/18°C versus 20/12°C) enhanced both C and N acquisition mainly because of an increase of both C assimilation in leaves and N absorption by roots, resulting in relatively constant C : N acquisition ratio. In addition, theTairandTrootinteraction was mainly observed in relative growth rate and root growth-related variables. Our results infer thatTairandTroothave distinct impacts on resource acquisition and carbon-nitrogen balance in plants.
Early Holocene morphological variation in hunter-gatherer hands and feet
Authors: Hoover Kara C. , Berbesque J. Colette
Published: February 2018

Background

The Windover mortuary pond dates to the Early Archaic period (6,800-5,200 years ago) and constitutes one of the earliest archaeological sites with intact and well-preserved human remains in North America. Unlike many prehistoric egalitarian hunter-gatherers, the Windover people may not have practiced a sex-based division of labor, rather they may have shared the load. We explore how mobility and subsistence, as reconstructed from archaeological data, influenced hand and foot bone morphology at Windover.

Methods

We took length and width measurements on four carpal bones, four tarsal bones, and load- bearing tarsal areas (calcaneus load arm, trochlea of the talus). We analyzed lateralization using side differences in raw length and width measurements. For other hypothesis testing, we used log transformed length-width ratios to mitigate the confounding effects of sexual dimorphism and trait size variation; we tested between-sex differences in weight-bearing (rear foot) and shock-absorbing (mid foot) tarsal bones and between-sex differences in carpal bones.

Results

We identified no significant between-sex differences in rear and midfoot areas, suggesting similar biomechanical stresses. We identified no significant between-sex differences in carpal bones but the test was under-powered due to small sample sizes. Finally, despite widespread behavioral evidence on contemporary populations for human hand and foot lateralization, we found no evidence of either handedness or footedness.

Discussion

The lack evidence for footedness was expected due its minimal impact on walking gait but the lack of evidence for handedness was surprising given that ethnographic studies have shown strong handedness in hunter-gatherers during tool and goods manufacture. The reconstructed activity patterns suggested both sexes engaged in heavy load carrying and a shared division of labor. Our results support previous findings—both sexes had stronger weight-bearing bones. While male shock-absorbing bones exhibited a trend towards greater relative width (suggesting greater comparative biomechanical stress), this may simply some lingering hunting behavior with males walking greater distances at higher speeds than females. While there were no significant between-sex differences in carpal bones (supporting a shared work load model), females exhibited greater variation in index values, which may reflect a greater variety of and specialization in tasks compared to males. Because carpals and tarsals are so well- preserved at archaeological sites, we had surmised they might be useful proxies for activity in the absence of well-preserved long bones. Tarsals provide a stronger signal of past activity and may be useful in the absence or, or in addition to, preferred bones. Carpals, however, may not be useful as the effect size of biomechanical stress (in this study at least) is low and would require larger samples than may be possible at archaeological sites.
Construction of whole genomes from scaffolds using single cell strand-seq data
Authors: Hills Mark , Falconer Ester , O’Neil Kieran , Sanders Ashley D. , Howe Kerstin , Guryev Victor , Lansdorp Peter M.
Published: February 2018

Accurate reference genome sequences provide the foundation for modern molecular biology and genomics as the interpretation of sequence data to study evolution, gene expression and epigenetics depends heavily on the quality of the genome assembly used for its alignment. Correctly organising sequenced fragments such as contigs and scaffolds in relation to each other is a critical and often challenging step in the construction of robust genome references. We previously identified misoriented regions in the mouse and human reference assemblies using Strand-seq, a single cell sequencing technique that preserves DNA directionality1, 2. Here we demonstrate the ability of Strand-seq to build and correct full-length chromosomes, by identifying which scaffolds belong to the same chromosome and determining their correct order and orientation, without the need for overlapping sequences. We demonstrate that Strand-seq exquisitely maps assembly fragments into large related groups and chromosome-sized clusters without using new assembly data. Using template strand inheritance as a bi-allelic marker, we employ genetic mapping principles to cluster scaffolds that are derived from the same chromosome and order them within the chromosome based solely on directionality of DNA strand inheritance. We prove the utility of our approach by generating improved genome assemblies for several model organisms including the ferret, pig, Xenopus, zebrafish, Tasmanian devil and the Guinea pig.
Genomic Signatures of Fine-Scale Local Adaptation in Atlantic Salmon Suggest Involvement of Sexual Maturation, Energy Homeostasis, Behaviour, and Immune Defence-Related Genes
Authors: Pritchard Victoria L. , Mäkinen Hannu , Vähä Juha-Pekka , Erkinaro Jaakko , Orell Panu , Primmer Craig R.
Published: February 2018

Elucidating the genetic basis of adaptation to the local environment can improve our understanding of how the diversity of life has evolved. In this study we used a dense SNP array to identify candidate loci underlying fine-scale local adaptation within a large Atlantic salmon (Salmo salar) population. By combining outlier, gene-environment association, and haplotype homozygosity analyses, we identified multiple regions of the genome with strong evidence for diversifying selection. Several of these candidate regions had previously been identified in other studies, demonstrating that the same loci be adaptively important in Atlantic salmon at sub-drainage, regional and continental scales. Notably, we identified signals consistent with local selection around genes associated with variation in sexual maturation, energy homeostasis, behaviour, and immune defence. These included the large-effect age-at-matunty genevgll3, the known obesity genemc4r, and major histocompatibility complex II. Most strikingly, we confirmed a genomic region on Ssa09 that was extremely differentiated among subpopulations, and that is also a candidate for local selection over the global range of Atlantic salmon. This region co-localized with a genomic region strongly associated with spawning ecotype in sockeye salmon (Oncorhynchus nerka), with circumstantial evidence that the same gene (six6) may be the selective target in both cases. The phenotypic effect of this region in Atlantic salmon remains cryptic, although allelic variation is related to river flow volume and co-vanes with timing of the return spawning migration. Our results further inform management of Atlantic salmon and open multiple avenues for future research.
Microzooplankton distribution in the Amundsen Sea Polynya (Antarctica) during an extensivePhaeocystis antarcticabloom
Authors: Swalethorp Rasmus , Dinasquet Julie , Logares Ramiro , Bertilsson Stefan , Kjellerup Sanne , Krabberød Anders K. , Moksnes Per-Olav , Nielsen Torkel G. , Riemann Lasse
Published: February 2018

In Antarctica, summer is a time of extreme environmental shifts resulting in large coastal phytoplankton blooms fueling the food web. Despite the importance of the microbial loop in remineralizing biomass from primary production, studies of how microzooplankton communities respond to such blooms in the Southern Ocean are rather scarce. Microzooplankton (ciliates and dinoflagellates) communities were investigated combining microscopy and 18S rRNA sequencing analyses in the Amundsen Sea Polynya during an extensive summer bloom ofPhaeocystis antarctica. The succession of microzooplankton was further assessed during a 15-day induced bloom microcosm experiment. Dinoflagellates accounted for up to 58% the microzooplankton biomassin situwithGymnodiniumspp.,Protoperidiumspp. andGyrodiniumspp. constituting 87% of the dinoflagellate biomass.Strombilidiumspp.,Strombidiumspp. and tintinids represented 90% of the ciliates biomass.Gymnodinium,Gyrodiniumand tintinnids are known grazers ofPhaeocystis,suggesting that this prymnesiophyte selected for the key microzooplankton taxa. Availability of other potential prey, such as diatoms, heterotrophic nanoflagellates and bacteria, also correlated to changes in microzooplankton community structure. Overall, both heterotrophy and mixotrophy appeared to be key trophic strategies of the dominant microzooplankton observed, suggesting that they influence carbon flow in the microbial food web through top-down control on the phytoplankton community.
Long-term live imaging of theDrosophilaadult midgut reveals real-time dynamics of cell division, differentiation, and loss
Authors: Martin Judy , Sanders Erin Nicole , Moreno-Roman Paola , Balachandra Shruthi , Du XinXin , Jaramillo Koyama Leslie Ann , O’Brien Lucy Erin
Published: February 2018

Organ renewal is governed by the dynamics of cell division, differentiation, and loss. To study these dynamics in real time, here we present a platform for extended live imaging of the adultDrosophilamidgut, a premier genetic model for stem cell-based organs. A window cut into a living animal allows the midgut to be imaged while intact and physiologically functioning. This approach prolongs imaging sessions to 12-16 hours and yields movies that document cell and tissue dynamics at vivid spatiotemporal resolution. Applying a pipeline for movie processing and analysis, we uncover new, intriguing cell behaviors: that mitotic stem cells dynamically re-orient, that daughter cells delay fate-determining Notch activation for many hours after birth, and that enterocytes extrude via constriction of a pulsatile cadherin ring. By enabling real-time study of cellular phenomena that were previously inaccessible, our platform opens a new realm for dynamic understanding of midgut organ renewal.
Delegating sex: differential gene expression in stolonizing syllids uncovers the hormonal control of reproduction in Annelida
Authors: Álvarez-Campos Patricia , Kenny Nathan J. , Verdes Aida , Fernández Rosa , Novo Marta , Giribet Gonzalo , Riesgo Ana
Published: February 2018

Stolonization in syllid annelids is a unique mode of reproduction among animals. During the breeding season, a structure resembling the adult but containing only gametes, called stolon, is formed at the posterior end of the animal. When the stolons mature, they detach from the adult and the gametes are released into the water column. The process is synchronized within each species, and it has been reported to be under environmental and endogenous control, probably via endocrine regulation. To further understand the reproduction in syllids and to elucidate the molecular toolkit underlying stolonization, we generated Illumina RNA-seq data from different tissues of reproductive and non-reproductive individuals ofSyllis magdalena, and characterized gene expression during the stolonization process. Several genes involved in gametogenesis (ovochymase,vitellogenin,testis-specific serine/threonine-kinase), immune response (complement receptor 2), neuronal development (tyrosine-protein kinase Src42A), cell proliferation (alpha-1D adrenergic receptor), and steroid metabolism (hydroxysteroid dehydrogenase2) were found differentially expressed in the different tissues and conditions analyzed. In addition, our findings suggest that several neurohormones, such as methyl farnesoate, dopamine and serotonin, might trigger the stolon formation, the correct maturation of gametes and the detachment of stolons when gametogenesis is complete. The process seems to be under circadian control, as indicated by the expression patterns ofr-opsins. Overall, our results shed light into the genes that orchestrate the onset of gamete formation, and improve our understanding of how some hormones, previously reported to be involved in reproduction and metamorphosis processes in other invertebrates, seem to also regulate reproduction via stolonization.