bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum
Authors: Schossig Anna , Haack Tobias , Kovács-Nagy Reka , Braunisch Matthias , Makowski Christine , Senderek Jan , Vill Katharina , Müller-Felber Wolfgang , Strom Tim , Krabichler Birgit , Freisinger Peter , Deshpande Charu , Polster Tilman , Wolf Nicole , Desguerre Isabelle , Wörmann Friedrich , Rötig Agnès , Ahting Uwe , Kopajtich Robert , Prokisch Holger , Meitinger Thomas , Feichtinger René , Mayr Johannes , Jungbluth Heinz , Hubmann Michael , Zschocke Johannes , Distelmaier Felix , Koch Johannes , Alhaddad Bader 
Published: June 2018

Background Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic PRUNE1 mutations.
Methods Linkage analysis and whole-exome sequencing (WES) in a multiplex family and extraction of further cases from a WES repository containing 571 children with severe developmental disabilities and neurologic symptoms.
Results We identified bi-allelic PRUNE1 mutations in twelve children from six unrelated families. All patients who survived beyond the first 6 months of life had early-onset global developmental delay, bilateral spastic paresis, dysphagia and difficult-to-treat seizures, while congenital or later-evolving microcephaly was not a consistent finding. Brain MRI showed variable anomalies with progressive cerebral and cerebellar atrophies and T2-hyperintense brain stem lesions. Peripheral neuropathy was documented in five cases. Disease course was progressive in all patients and eight children died in the first or early second decade of life. In addition to the previously reported missense mutation p.(Asp106Asn), we observed a novel homozygous missense variant p.(Leu172Pro) and a homozygous contiguous gene deletion encompassing most of the PRUNE1 gene and part of the neighboring BNIPL gene.
Conclusions PRUNE1 deficiency causes severe early-onset disease affecting the central and peripheral nervous systems. Microcephaly is probably not a universal feature.
Computer simulations of Jupiter’s deep internal dynamics help interpret what Juno sees
Authors: Glatzmaier Gary A. 
Published: June 2018

Significance
NASA’s Juno spacecraft is currently orbiting Jupiter, collecting high-fidelity measurements of its near surface. The resulting patterns of magnetic and gravity fields above Jupiter’s surface have already started providing insight into the type of winds in Jupiter’s deep interior. In addition, by monitoring cloud motions on Jupiter’s surface, Juno may detect a particular type of wave with properties that could tell us the size of Jupiter’s small rocky core. Here, we describe 3D time-dependent computer simulations of thermal convection and magnetic field generation in Jupiter’s deep interior that will help interpret and explain the maintenance of these global near-surface patterns that Juno continues to measure.
Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth
Authors: Pacella Ilenia , Procaccini Claudio , Focaccetti Chiara , Miacci Stefano , Timperi Eleonora , Faicchia Deriggio , Severa Martina , Rizzo Fabiana , Coccia Eliana Marina , Bonacina Fabrizia , Mitro Nico , Norata Giuseppe Danilo , Rossetti Grazisa , Ranzani Valeria , Pagani Massimiliano , Giorda Ezio , Wei Yu , Matarese Giuseppe , Barnaba Vincenzo , Piconese Silvia 
Published: June 2018

Significance
Recent studies have established that metabolic restrains, such as glucose restriction, impair the activities of effector T cells in the tumor microenvironment. In the same context, a huge expansion of activated Treg cells in tumor tissues has been described in mice and humans, contributing to the suppression of protective antitumor immunity. Our data demonstrate that Tregs are committed to survive and proliferate in such a hostile milieu thanks to a metabolic advantage based on the combination of glycolysis and fatty acid synthesis and oxidation. This allows Tregs to prevail over conventional T cells that rely primarily on the glycolytic pathway for their metabolic demands. Awareness of the metabolic dynamics of Tregs in tumor could provide a means for cancer immunotherapy.
Multigenome analysis implicates miniature inverted-repeat transposable elements (MITEs) in metabolic diversification in eudicots
Authors: Boutanaev Alexander M. , Osbourn Anne E. 
Published: June 2018

SignificanceRecently discovered biosynthetic gene clusters in plants are a striking example of the nonrandom complex structure of eukaryotic genomes. The mechanisms underpinning the formation of these clustered pathways are not understood. Here we carry out a systematic analysis of transposable elements associated with clustered terpene biosynthetic genes in plant genomes, and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Our analyses provide insights into potential mechanisms of cluster assembly. They also shed light on the emergence of a “block” mechanism for the foundation of new terpene clusters in the eudicots in which microsyntenic blocks of terpene synthase and cytochrome P450 gene pairs duplicate, providing templates for the evolution of new pathways.
Enhancement of Ebola virus infection by seminal amyloid fibrils
Authors: Bart Stephen M. , Cohen Courtney , Dye John M. , Shorter James , Bates Paul 
Published: June 2018

Significance
During the 2014–2016 Ebola outbreak, multiple instances of male-to-female sexual transmission of Ebola virus (EBOV) were reported. While relatively uncommon, EBOV sexual transmission presents a major public health concern, as these transmission events occurred months after recovery. Further, sexual transmission was linked to a resurgence of EBOV disease in Guinea, which had previously been declared Ebola-free. However, the role of host factors involved in sexual transmission remains unknown. We find that seminal amyloids and semen greatly enhance EBOV infection and alter the virion physical properties, stabilizing viral infectivity and protecting the virus from drying. These results promote seminal amyloids as possible targets for intervention to prevent EBOV sexual transmission and seeding new infection chains that reignite an outbreak.
Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory
Authors: Gould Joanna M. , Smith Phoebe J. , Airey Chris J. , Mort Emily J. , Airey Lauren E. , Warricker Frazer D. M. , Pearson-Farr Jennifer E. , Weston Eleanor C. , Gould Philippa J. W. , Semmence Oliver G. , Restall Katie L. , Watts Jennifer A. , McHugh Patrick C. , Smith Stephanie J. , Dewing Jennifer M. , Fleming Tom P. , Willaime-Morawek Sandrine 
Published: June 2018

Significance
Maternal protein malnutrition during pregnancy and lactation compromises brain development, with lasting consequences for motor and cognitive function. However, the importance of nutrition on early brain development is unknown. We have previously shown that maternal low-protein diet confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotor behavioral abnormalities in adult offspring. Here, we report that Emb-LPD and sustained LPD reduce neural stem cells (NSCs) in the fetal brain. Moreover, Emb-LPD causes remaining NSCs to upregulate neuronal differentiation in compensation beyond control levels and increase cortex thickness and neuron ratio, leading to adult memory deficits. These data demonstrate that poor maternal nutrition from conception adversely affects brain development and adult memory.
Degradation of unmethylated miRNA/miRNA*s by a DEDDy-type 3′ to 5′ exoribonuclease Atrimmer 2 in
Arabidopsis
Authors: Wang Xiaoyan , Wang Yuan , Dou Yongchao , Chen Lu , Wang Junli , Jiang Ning , Guo Chunce , Yao Qingqing , Wang Chizao , Liu Lin , Yu Bin , Zheng Binglian , Chekanova Julia A. , Ma Jinbiao , Ren Guodong 
Published: June 2018

Significance
The steady-state levels of miRNAs are under sophisticated control to ensure their proper functions such as development and responses to environmental stimuli. Nevertheless, enzymes responsible for the degradation of various forms of unmethylated miRNAs remain enigmatic, which largely impedes our understanding of miRNA homeostasis and active turnover. Here we report a 3′ to 5′ exoribonuclease Atrimmer 2 that may degrade unmethylated miRNAs in their miRNA/miRNA* duplex status, at places distinct from their production sites (i.e., Dicing bodies). Our study not only increases the complexity of miRNA surveillance, but also provides clues into how nascent miRNA/miRNA* duplexes undergo methylation and RNA-induced silencing complex loading, which is a big challenge in the plant small RNA field.
Ionic liquids for oral insulin delivery
Authors: Banerjee Amrita , Ibsen Kelly , Brown Tyler , Chen Renwei , Agatemor Christian , Mitragotri Samir 
Published: June 2018

Significance
Insulin is currently available as an injectable formulation, but an oral product would enjoy higher patient compliance and would significantly improve the quality of life of diabetic patients worldwide. However, oral delivery of proteins such as insulin is challenging due to various gastrointestinal barriers to oral absorption of macromolecules. We have developed a safe and highly effective ionic liquid-based oral insulin formulation that significantly enhanced oral insulin absorption by efficiently circumventing the gastrointestinal barriers. Besides, the formulation demonstrated good stability at room temperature and under refrigeration. Evidence from cell and animal studies supports a promising prospect of development of the formulation into a clinical product.
Coupled laboratory and field investigations resolve microbial interactions that underpin persistence in hydraulically fractured shales
Authors: Borton Mikayla A. , Hoyt David W. , Roux Simon , Daly Rebecca A. , Welch Susan A. , Nicora Carrie D. , Purvine Samuel , Eder Elizabeth K. , Hanson Andrea J. , Sheets Julie M. , Morgan David M. , Wolfe Richard A. , Sharma Shikha , Carr Timothy R. , Cole David R. , Mouser Paula J. , Lipton Mary S. , Wilkins Michael J. , Wrighton Kelly C. 
Published: June 2018

Significance
Microorganisms persisting in hydraulically fractured shales must maintain osmotic balance in hypersaline fluids, gain energy in the absence of electron acceptors, and acquire carbon and nitrogen to synthesize cell building blocks. We provide evidence that that cofermentation of amino acids (Stickland reaction) meets all of these organismal needs, thus functioning as a keystone metabolism in enriched and natural microbial communities from hydraulically fractured shales. This amino acid-based metabolic network can be rationally designed to optimize biogenic methane yields and minimize undesirable chemistries in this engineered ecosystem. Our proposed ecological framework extends to the human gut and other protein-rich ecosystems, where the role of Stickland fermentations and their derived syntrophies play unrecognized roles in carbon and nitrogen turnover.
Fisheries bycatch risk to marine megafauna is intensified in Lagrangian coherent structures
Authors: Scales Kylie L. , Hazen Elliott L. , Jacox Michael G. , Castruccio Frederic , Maxwell Sara M. , Lewison Rebecca L. , Bograd Steven J. 
Published: June 2018

SignificanceMarine capture fisheries provide a valuable source of protein and are economically important in coastal communities. However, fisheries sustainability is impacted by incidental capture of nontarget species (bycatch), which remains a major global threat to marine megafauna such as sharks, sea turtles, seals, cetaceans, and seabirds. Understanding where and when bycatch events take place can guide fisheries sustainability solutions. Here, we model how dynamic structures in the ocean such as fronts and eddies influence fisheries effort, catch, and bycatch likelihood. We find that bycatch of a diverse range of species is more likely in attracting Lagrangian coherent structures, in which water masses meet and aggregate prey, predators, and fishers into hotspots of risk.
ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma
Authors: Pieraccioli Marco , Nicolai Sara , Pitolli Consuelo , Agostini Massimiliano , Antonov Alexey , Malewicz Michal , Knight Richard A. , Raschellà Giuseppe , Melino Gerry 
Published: June 2018

Significance
High-risk neuroblastomas (NBs) show undifferentiated/poorly differentiated morphology as a distinctive feature. We have identified the transcription factor ZNF281 as a factor that can counteract the neuronal differentiation of primary neurons in culture and NB cells. The expression of ZNF281 is inhibited by TAp73 and promoted by MYCN. In turn, ZNF281 inhibits the expression of GDNF and NRP2, two proteins associated with neuronal differentiation. In patients with NB, the expression of ZNF281 is higher in high-risk patients and is associated with worse prognosis. Understanding the molecular mechanisms that regulate neuronal differentiation is relevant for the identification of defects in this process that underlie the development of tumors such as NB, in which an aberrant differentiation arrest has occurred.
Structure of the Lassa virus glycan shield provides a model for immunological resistance
Authors: Watanabe Yasunori , Raghwani Jayna , Allen Joel D. , Seabright Gemma E. , Li Sai , Moser Felipe , Huiskonen Juha T. , Strecker Thomas , Bowden Thomas A. , Crispin Max 
Published: June 2018

Significance
Lassa virus is a highly pathogenic arenavirus that causes severe hemorrhagic fever in humans. Currently, there are no efficacious vaccines or treatments available to combat this pathogen. An important component of any vaccine candidate against Lassa virus will likely include the highly glycosylated glycoprotein complex presented on the virion surface. Here, we determine the composition of the Lassa virus glycome, revealing that the virus presents an abundance of glycans that are not biosynthetically processed to full maturity. Such underprocessed glycans form spatially distinct clusters, which shield the proteinous surface of the Lassa virus glycoprotein spike from the humoral immune response. These data are integral for the development of humoral-based vaccines that mimic the mature Lassa virion.
Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis
Authors: Clark Ryan R. , Judd Julius , Lasek-Nesselquist Erica , Montgomery Sarah A. , Hoffmann Jennifer G. , Derbyshire Keith M. , Gray Todd A. 
Published: June 2018

SignificanceA conjugation model of mycobacterial interaction recently revealed that intercellular communication occurs between donors and recipients. This communication links two ESAT-6 (ESX) (type VII) secretion systems that are both required for conjugation. Functionally distinct ESX secretion systems are found in all mycobacteria, and they serve important virulence functions in pathogenic mycobacteria. We demonstrate that SigM, an extracytoplasmic transcription factor, activates ESX-4. Direct donor-recipient cell contact triggers the recipient cell to release membrane-sequestered SigM, which rapidly induces an ESX-4-focused regulon. The conservation of SigM and ESX-4 throughout mycobacteria suggests that this interaction-response network is intact and active in pathogens. Contact-dependent responses similar to those identified in our model system may therefore also mediate communal processes within infectious mycobacterial populations.
Reversible inhibition of the ClpP protease via an N-terminal conformational switch
Authors: Vahidi Siavash , Ripstein Zev A. , Bonomi Massimiliano , Yuwen Tairan , Mabanglo Mark F. , Juravsky Jordan B. , Rizzolo Kamran , Velyvis Algirdas , Houry Walid A. , Vendruscolo Michele , Rubinstein John L. , Kay Lewis E. 
Published: June 2018

Significance
ClpP is a protease that degrades damaged or misfolded proteins. Consistent with its critical role in maintaining cellular homeostasis, inhibiting and dysregulating ClpP function has shown promise in fighting antibiotic resistance and in targeting cancer cells in acute myeloid leukemia. Here we identify a conformational switch in ClpP that, upon mutagenesis, leads to a catalytically inactive structure that can be reactivated through the binding of small-molecule activators. This functional hotspot therefore represents a drug target for allosteric inhibition of ClpP. The combination of methyl–transverse relaxation-optimized spectroscopy (TROSY) NMR, cryo-EM, and molecular simulation methods employed here provides a detailed characterization of ClpP along with the promise of crucial insights into the structure–function relationship of molecular machines in general.
The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease
Authors: Sherrer Shanen M. , Penland Elisabeth , Modrich Paul 
Published: June 2018

Significance
MutLα (MLH1-PMS2 heterodimer) is an endonuclease that acts during an early step of eukaryotic mismatch repair. We show that human MutLα endonuclease copurifies with two equivalents of bound zinc, at least one of which resides within the endonuclease active site. We also show that cadmium, a known inhibitor of zinc-dependent enzymes and a potent mutagen and carcinogen, is a high-affinity inhibitor of MutLα endonuclease and that exogenous MutLα significantly reverses the mismatch repair defect in cadmium-treated human cell nuclear extract or nuclear extract prepared from cadmium-treated cells. Because the mutagenic action of cadmium is largely due to the selective inhibition of mismatch repair, these findings suggest that MutLα is a primary cadmium target for mutagenesis and presumably, carcinogenesis as well.
A Prospective Pilot Study Comparing Rate of Processing Techniques in Autologous Fat Grafting
Authors: Hanson Summer E , Garvey Patrick B , Chang Edward I , Reece Gregory , Liu Jun , Butler Charles E 
Published: June 2018

AbstractBackgroundAutologous fat grafting (AFG) is increasing in popularity to address a variety of defects. There is interest in developing techniques to harvest, process, and inject fat to improve clinical outcomes as well as operative efficiency.ObjectivesThe purpose of this pilot study is to compare the rate of graft processing of two commercially available systems for graft preparation.MethodsTwenty consecutive cases using an active filtration system (system-AF) were observed followed by 20 consecutive cases using a passive filtration system (system-PF) to compare efficiency rate. Fat processing rate was quantified in milliliters/minute.ResultsForty patients underwent AFG with no differences in patient characteristics between the groups. There was 1 incidence of palpable fat necrosis per group (5%). For all patients, this was the first fat grafting procedure; 20% of patients (n = 4 per group) had additional fat grafting. Overall, the rate of adipose tissue preparation was significantly higher with system-AF compared to system-PF (19.8 mL/min vs 5.3 mL/min, P ≤ 0.001). The resulting percent of graftable fat was comparable (AF: 41% vs PF: 42%; P = 0.83).ConclusionsTime and motion studies such as this provide a means to systematically document each of the steps involved in fat grafting in a reliable fashion. The authors demonstrate a significantly higher rate of lipoaspirate processing using an active filtration system compared to a passive system. Further large-scale studies of the efficacy and cost analysis of AFG are a necessary component of determining best practices in the field.Level of Evidence: 2
Intraneural IFG-1 in Cryopreserved Nerve Isografts Increase Neural Regeneration and Functional Recovery in the Rat Sciatic Nerve
Authors: González Porto Sara Alicia , Domenech Nieves , Blanco Francisco J , Centeno Cortés Alberto , Rivadulla Fernández Casto , Álvarez Jorge Ángel , Sánchez Ibáñez Jacinto , Rendal Vázquez Esther 
Published: June 2018

Abstract

BACKGROUND
Insulin-like growth factor 1 (IGF-1) was found to stimulate Schwann cell mitosis. Exogenous IGF-1 may improve nerve regeneration after cryopreservation.

OBJECTIVE
To evaulate the effect of intraneural administration of IGF-1 in cryopreserved nerve isografts.

METHODS
Eighteen millimeter grafts were used for bridging an 18-mm defect in the rat sciatic nerve. A total of 57 rats were randomly divided into three groups: (1) autograft (Group 1); (2) cryopreserved isograft (Group 2); (3) cryopreserved isograft with intraneural IGF-1 administration (Group 3). 12 weeks after surgery, functional recovery (Sciatic functional index [SFI], Swing speed [SS], nerve conduction velocity [NCV], amplitude of compound motor action potentials [CMAP], and gastrocnemius muscle index [GMI]) and nerve regeneration (myelin sheath area, total fiber counts, fiber density, and fiber width) were all evaluated.

RESULTS
The intraneural injection of IGF-1 significantly improved SFI and SS at weeks 10 and 12. There were no statistical differences between Groups 1 and 3 in any of the SFI or SS evaluations. CMAP and NCV in Group 1 were significantly higher than in Groups 2 and 3, and Group 3 had significantly higher CMAP and NCV compared to Group 2. No significant differences were found in fiber width. The number of nerve fibers, percentage of myelinated fibers, fiber density, and GMI was significantly higher in Group 1 compared to Group 2, but no significant differences were found between Groups 1 and 3.

CONCLUSION
The results show that intraneural injection of IGF-1 in an 18 mm cryopreserved isograft improve axonal regeneration and functional recovery.