bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of adverse pregnancy outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction
Authors: Monaghan C. , Kalafat E. , Binder J. , Thilaganathan B. , Khalil A.
Published: April 2018

Objective

To identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR).

Methods

This was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin–twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end‐diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV‐PIV) were converted to Z‐scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin.

Results

We analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type‐I and 38 (36.5%) with Type‐II sFGR at initial presentation. In pregnancies complicated by Type‐II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type‐I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type‐II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth‐weight centile of the smaller twin (P < 0.01), those with Type‐I sFGR had earlier GA at delivery (P = 0.007) and those with Type‐II sFGR had higher DV‐PIV Z‐score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type‐I or Type‐II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56–0.88); P = 0.002), Type‐II sFGR (HR, 3.53 (95% CI, 1.37–9.07); P = 0.008) and higher DV‐PIV Z‐score (HR, 1.36 (95% CI, 1.12–1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin.

Conclusions

Pregnancies complicated by Type‐II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type‐I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type‐I or Type‐II sFGR. Earlier GA at diagnosis, Type‐II sFGR and higher DV‐PIV Z‐score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Cuckoo search for wind farm optimization with auxiliary infrastructure
Authors: Afanasyeva Svetlana , Saari Jussi , Pyrhönen Olli , Partanen Jarmo
Published: May 2018

This paper focuses on the optimization problem of a wind farm layout. This area of research is currently receiving widespread attention, as optimal positioning of the turbines promotes the financial viability of the wind farm and enhances the competitiveness of wind projects in the energy market. In this work, cuckoo search (CS), a modern population‐based metaheuristic optimization algorithm, is used. The objective is to find the turbine layout and types that maximize the net present value of the wind farm, while constraints on the turbine positions have to be met. The following constraints are considered: Firstly, the minimum distance between turbines for safe operation; secondly, a realistic wind farm shape including forbidden zones for installation and the existing infrastructure. Furthermore, the optimization of the wind farm includes an algorithm to find the least expensive layout of the wind farm roads and the electrical collector system. The algorithm is based on Dijkstra's shortest path and Prim's minimum spanning tree algorithms. The test results indicate that the infrastructure cost has a significant effect on the optimum wind farm solution. A genetic algorithm, commonly applied to wind farm micro‐siting problems, is used to benchmark the performance of the CS. The results show that the CS is capable of consistently finding better solutions than the genetic algorithm.
Medical Care, Social Determinants of Health, and Health Equity
Authors: Marmot Michael
Published: May 2018

Sir Michael Marmot writes on public health, social determinants of health, and health equity.
LARP1 on TOP of ribosome production
Authors: Fonseca Bruno D. , Lahr Roni M. , Damgaard Christian K. , Alain Tommy , Berman Andrea J.
Published: May 2018

The ribosome is an essential unit of all living organisms that commands protein synthesis, ultimately fuelling cell growth (accumulation of cell mass) and cell proliferation (increase in cell number). The eukaryotic ribosome consists of 4 ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs). Despite its fundamental role in every living organism, our present understanding of how higher eukaryotes produce the various ribosome components is incomplete. Uncovering the mechanisms utilized by human cells to generate functional ribosomes will likely have far‐reaching implications in human disease. Recent biochemical and structural studies revealed La‐related protein 1 (LARP1) as a key new player in RP production. LARP1 is an RNA‐binding protein that belongs to the LARP superfamily; it controls the translation and stability of the mRNAs that encode RPs and translation factors, which are characterized by a 5′ terminal oligopyrimidine (5′TOP) motif and are thus known as TOP mRNAs. The activity of LARP1 is regulated by the mammalian target of rapamycin complex 1 (mTORC1): a eukaryotic protein kinase complex that integrates nutrient sensing with mRNA translation, particularly that of TOP mRNAs. In this review, we provide an overview of the role of LARP1 in the control of ribosome production in multicellular eukaryotes.

This article is categorized under:

Translation > Translation Regulation

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

RNA Processing > Capping and 5′ End Modifications
Use of somatic cell banks in the conservation of wild felids
Authors: Praxedes Érika A. , Borges Alana A. , Santos Maria V.O. , Pereira Alexsandra F.
Published: May 2018

The conservation of biological resources is an interesting strategy for the maintenance of biodiversity, especially for wild felids who are constantly threatened with extinction. For this purpose, cryopreservation techniques have been used for the long‐term storage of gametes, embryos, gonadal tissues, and somatic cells and tissues. The establishment of these banks has been suggested as a practical approach to the preservation of species and, when done in tandem with assisted reproductive techniques, could provide the means for reproducing endangered species. Somatic cell banks have been shown remarkable for the conservation of genetic material of felids; by merely obtaining skin samples, it is possible to sample a large group of individuals without being limited by factors such as gender or age. Thus, techniques for somatic tissue recovery, cryopreservation, and in vitro culture of different wild felids have been developed, resulting in a viable method for the conservation of species. One of the most notable conservation programs for wild felines using somatic samples was the one carried out for the Iberian lynx, the most endangered feline in the world. Other wild felids have also been studied in other continents, such as the jaguar in South America. This review aims to present the technical progress achieved in the conservation of somatic cells and tissues in different wild felids, as well address the progress that has been achieved in a few species.
Thermal dark matter co-annihilating with a strongly interacting scalar
Authors: Biondini S. , Laine M.
Published: April 2018

Abstract

Recently many investigations have considered Majorana dark matter co-annihilating with bound states formed by a strongly interacting scalar field. However only the gluon radiation contribution to bound state formation and dissociation, which at high temperatures is subleading to soft 2 → 2 scatterings, has been included. Making use of a non-relativistic effective theory framework and solving a plasma-modified Schrödinger equation, we address the effect of soft 2 → 2 scatterings as well as the thermal dissociation of bound states. We argue that the mass splitting between the Majorana and scalar field has in general both a lower and an upper bound, and that the dark matter mass scale can be pushed at least up to 5…6TeV.
Liberty Asthma QUEST: Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Dupilumab Efficacy/Safety in Patients with Uncontrolled, Moderate-to-Severe Asthma
Authors: Busse William W. , Maspero Jorge F. , Rabe Klaus F. , Papi Alberto , Wenzel Sally E. , Ford Linda B. , Pavord Ian D. , Zhang Bingzhi , Staudinger Heribert , Pirozzi Gianluca , Amin Nikhil , Akinlade Bolanle , Eckert Laurent , Chao Jingdong , Graham Neil M. H. , Teper Ariel
Published: May 2018

Introduction

Dupilumab, a fully human anti-IL-4Rα monoclonal antibody, inhibits signaling of both interleukin (IL)-4 and IL-13, which are key drivers of type 2-mediated inflammation. Dupilumab is approved in the EU, USA, and other countries for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. Following positive phase 2 results in asthma, the phase 3 Liberty Asthma QUEST trial was initiated to provide further evidence for dupilumab efficacy and safety in patients with uncontrolled, moderate-to-severe asthma.

Methods

Liberty Asthma QUEST is a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (NCT02414854) in patients with persistent asthma who are receiving continuous treatment with inhaled corticosteroids (ICS) plus one or two other asthma controller medicines. A total of 1902 patients (aged ≥ 12 years) were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on therapy with subcutaneously administered dupilumab 200 or 300 mg every 2 weeks or matched placebo. The study consisted of a 4 ± 1-week screening period, 52-week randomized treatment period, and 12-week post-treatment follow-up period. All patients continued to receive their prescribed ICS plus up to two additional controller medications. The primary efficacy endpoints were annualized rate of severe exacerbation events during the 52-week treatment period and absolute change from baseline in pre-bronchodilator FEV1 at week 12.

Conclusion

Uncontrolled asthma patients with persistent symptoms represent a population of significant unmet need, for whom new treatments are required. Patients with severe asthma are at high risk of asthma exacerbations, and face an accelerated decline in lung function and impaired quality of life. QUEST examines the efficacy of dupilumab in this at-risk patient population; it is the largest placebo-controlled study in uncontrolled, moderate-to-severe asthma with a biologic agent to date, and the only phase 3 study of a biologic therapy of asthma that enrolled patients irrespective of baseline type 2 inflammatory biomarker levels.

Funding

Sanofi and Regeneron Pharmaceuticals, Inc.

Clinical Trials.gov Identifier

NCT02414854.
Comparative Analysis of Human Genes Frequently and Occasionally Regulated by m6A Modification
Authors: Zhou Yuan , Cui Qinghua
Published: May 2018

The m6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m6A modification (m6Afreq genes) and those occasionally regulated by m6A modification (m6Aocca genes). Compared to the m6Aocca genes, the m6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein–protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m6A epitranscriptomic regulation and other gene expression regulatory machineries.
SPORTS1.0: A Tool for Annotating and Profiling Non-Coding RNAs Optimized for rRNA- and tRNA-Derived Small RNAs
Authors: Shi Junchao , Ko Eun-A , Sanders Kenton M. , Chen Qi , Zhou Tong
Published: May 2018

High-throughput RNA-seq has revolutionized the process of small RNA (sRNA) discovery, leading to a rapid expansion of sRNA categories. In addition to the previously well-characterized sRNAs such as microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNA (snoRNAs), recent emerging studies have spotlighted on tRNA-derived sRNAs (tsRNAs) and rRNA-derived sRNAs (rsRNAs) as new categories of sRNAs that bear versatile functions. Since existing software and pipelines for sRNA annotation are mostly focused on analyzing miRNAs or piRNAs, here we developed the sRNA annotation pipeline  optimized for rRNA- and tRNA-derived sRNAs (SPORTS1.0). SPORTS1.0 is optimized for analyzing tsRNAs and rsRNAs from sRNA-seq data, in addition to its capacity to annotate canonical sRNAs such as miRNAs and piRNAs. Moreover, SPORTS1.0 can predict potential RNA modification sites based on nucleotide mismatches within sRNAs. SPORTS1.0 is precompiled to annotate sRNAs for a wide range of 68 species across bacteria, yeast, plant, and animal kingdoms, while additional species for analyses could be readily expanded upon end users’ input. For demonstration, by analyzing sRNA datasets using SPORTS1.0, we reveal that distinct signatures are present in tsRNAs and rsRNAs from different mouse cell types. We also find that compared to other sRNA species, tsRNAs bear the highest mismatch rate, which is consistent with their highly modified nature. SPORTS1.0 is an open-source software and can be publically accessed at https://github.com/junchaoshi/sports1.0.
Observation of the seismoelectric effect in a gas condensate field in the Earth’s natural electromagnetic and seismic noise of 0.1–20 Hz
Authors: Shaidurov G.Ya. , Kudinov D.S. , Potylitsyn V.S. , Shaidurov R.G.
Published: May 2018

The first experimental measurements of the cross-correlation function (CCF) of the Earth’s seismic and electrical noise were carried out in two areas of the Minusinskoe gas condensate field in 2014 and 2015 using a VPEMPZ-M1 (Shum-6) two-channel geophysical device developed at Siberian Federal University. The Earth’s seismic noise and electrical noise in the frequency range 0.1–20 Hz were received by a geophone and an electric dipole, respectively. In both cases, a productive pool at depths of 1800–2000 m had a maximum CCF value five to seven times higher than the normal background, indicating the occurrence of the seismoelectric effect in passive fields.
Lifestyle and neurodegeneration in midlife as expressed on functional magnetic resonance imaging: A systematic review
Authors: Topiwala Hinesh , Terrera Graciela Muniz , Stirland Lucy , Saunderson Kathryn , Russ Tom C. , Dozier Marshall F. , Ritchie Craig W.
Published: May 2018

Introduction

Lifestyle factors may influence brain health in midlife. Functional magnetic resonance imaging is a widely used tool to investigate early changes in brain health, including neurodegeneration. In this systematic review, we evaluate the relationship between lifestyle factors and neurodegeneration in midlife, as expressed using functional magnetic resonance imaging.

Methods

We searched MEDLINE, EMBASE, and PsycINFO combining subject headings and free text terms adapted for each database. Articles were screened, and their quality was assessed independently by two reviewers before final inclusion in the review.

Results

We screened 4116 studies and included 29 in the review. Seven lifestyle factors, such as alcohol, cognitive training, excessive internet use, fasting, physical training, smoking, and substance misuse, were identified in this review.

Discussion

Cognitive and physical trainings appear to be associated with a neuroprotective effect, whereas alcohol misuse, smoking, and substance misuse appear to be associated with neurodegeneration. Further research is required into the effects of excessive internet use and fasting.
Editorial
Authors: Barrett Steve
Published: May 2018

Toyota is certainly using its industrial might to lead the global charge towards wider use of fuel cell and hydrogen technologies.
THE COMPLEXITY OF THOMASON’S ALGORITHM FOR FINDING A SECOND HAMILTONIAN CYCLE
Authors: ZHONG LIANG
Published: May 2018

By Smith’s theorem, if a cubic graph has a Hamiltonian cycle, then it has a second Hamiltonian cycle. Thomason [‘Hamilton cycles and uniquely edge-colourable graphs’, Ann. Discrete Math.3 (1978), 259–268] gave a simple algorithm to find the second cycle. Thomassen [private communication] observed that if there exists a polynomially bounded algorithm for finding a second Hamiltonian cycle in a cubic cyclically 4-edge connected graph $G$, then there exists a polynomially bounded algorithm for finding a second Hamiltonian cycle in any cubic graph $G$. In this paper we present a class of cyclically 4-edge connected cubic bipartite graphs $G_{i}$ with $16(i+1)$ vertices such that Thomason’s algorithm takes $12(2^{i}-1)+3$ steps to find a second Hamiltonian cycle in $G_{i}$.
FEW-WEIGHT CODES FROM TRACE CODES OVER
Authors: SHI MINJIA , GUAN YUE , WANG CHENCHEN , SOLÉ PATRICK
Published: May 2018

We construct two families of few-weight codes for the Lee weight over the ring $R_{k}$ based on two different defining sets. For the first defining set, taking the Gray map, we obtain an infinite family of binary two-weight codes which are in fact $2^{k}$-fold replicated MacDonald codes. For the second defining set, we obtain two infinite families of few-weight codes. These few-weight codes can be used to implement secret-sharing schemes.
Right on Schedule: CEO Option Grants and Opportunism
Authors: Daines Robert M. , McQueen Grant R. , Schonlau Robert J.
Published: May 2018

After the public outcry over backdating, many firms began scheduling option grants. This eliminates backdating but creates other agency problems: Chief executive officers (CEOs) aware of upcoming option grants have an incentive to temporarily depress stock prices to obtain lower strike prices. We show that some CEOs have manipulated stock prices to increase option compensation, documenting negative abnormal returns before scheduled option grants and positive abnormal returns afterward. These returns are explained by measures of CEOs’ incentives and ability to influence stock prices. We document several mechanisms used to lower stock price, including changing the substance and timing of disclosures.
Submandibular gland invasion and feasibility of gland-sparing neck dissection in oral cavity carcinoma
Authors: Cakir Cetin A , Dogan E , Ozay H , Kumus O , Erdag T K , Karabay N , Sarioglu S , Ikiz A O
Published: May 2018

Objective:

This study investigated the incidence and routes of submandibular gland involvement in oral cavity carcinoma to determine the feasibility of submandibular gland sparing neck dissection.

Methods:

The records of 155 patients diagnosed with oral cavity squamous cell carcinoma, with a total of 183 neck specimens, including those involving level I, were reviewed retrospectively.

Results:

Submandibular gland involvement, via direct invasion from the anatomical proximity of T4a tumours, was evident in two patients. The floor of mouth location, either primarily or as an extension of the primary tumour, was the only risk factor for submandibular gland involvement in oral cavity carcinoma (p = 0.042). Tumour location, clinical and pathological tumour (T) and nodal (N) stages, and radiological suspicion of mandible invasion, were not found to be statistically relevant (p > 0.05).

Conclusion:

The results suggest the feasibility of preserving the submandibular gland in early stage oral cavity carcinoma unless the tumour is located in, or extends to, the floor of mouth.
The Politics of Disembarkation: Empire, Shipping and Labor in the Port of Durban, 1897–1947
Authors: Hyslop Jonathan
Published: May 2018

This article examines the labor politics of race in Durban harbor between 1897 and 1947. It approaches the subject from an analysis of labor in a global, and particularly a British Empire, context. The article aims to move away from a solely “national” focus on the South African state and instead to look “up” toward connections to the British Empire, the world economy, and global social and political movements, and “down” towards Durban itself. These large scale (imperial and global) and small scale (city) levels were very concretely connected by Durban's role as a port. This article contends that in order to understand the place of working class Durban in an imperial world, we need to incorporate the shipping industry into other labor histories, studying how the movement of vessels and the actions of seafarers concretely linked these spatial levels. This article provides a broad overview of the sociological “shape” of the Durban working class and focuses on four “moments” of racialized labor in Durban harbor: the riot against M.K. Gandhi in 1897, the British seamen's strike of 1925, the insurgency of black dockworkers in the late 1920s and early 1930s, and the conflicts over the presence of Indian seamen in the port during the Second World War. These events revolved around what is here called a politics of disembarkation, in which the joining of the ship to the world of the shore created a zone of conflict.
Academic Casualization in the UK
Authors: Parfitt Steven
Published: May 2018

The casualization of academic work is a deepening problem at UK universities. From the late 1990s, the number of academics working on non-permanent, non-full-time contracts has skyrocketed, even as student fees have increased at an exponential rate. This casualization has generated resistance on the lower rungs of the academic ladder. On the one hand, the union for the higher education sector, the UCU, has tried without much success to stem the tide of casualization. On the other, casual academic staff have tried to organise on their own to resist casualization at a local level.
Geochemical Evidence for Large‐Scale Drainage Reorganization in Northwest Africa During the Cretaceous
Authors: Mourlot Yannick , Roddaz Martin , Dera Guillaume , Calvès Gérôme , Kim Jung‐Hyun , Chaboureau Anne‐Claire , Mounic Stéphanie , Raisson François
Published: April 2018

West African drainage reorganization during Cretaceous opening of the Atlantic Ocean is deciphered here from geochemical provenance studies of Central Atlantic sediments. Changes in the geochemical signature of marine sediments are reflected in major and trace element concentrations and strontium‐neodymium radiogenic isotopic compositions of Cretaceous sedimentary rocks from eight Deep Sea Drilling Project (DSDP) sites and one exploration well. Homogeneous major and trace element compositions over time indicate sources with average upper (continental) crust signatures. However, detailed information on the ages of these sources is revealed by neodymium isotopes (expressed as ɛNd). The ɛNd(0) values from the DSDP sites show a three‐step decrease during the Late Cretaceous: (1) the Albian‐Middle Cenomanian ɛNd(0) values are heterogeneous (–5.5 to −14.9) reflecting the existence of at least three subdrainage basins with distinct sedimentary sources (Hercynian/Paleozoic, Precambrian, and mixed Precambrian/Paleozoic); (2) during the Late Cenomanian‐Turonian interval, ɛNd(0) values become homogeneous in the deepwater basin (–10.3 to −12.4), showing a negative shift of 2 epsilon units interpreted as an increasing contribution of Precambrian inputs; (3) this negative shift continues in the Campanian‐Maastrichtian (ɛNd(0) = −15), indicating that Precambrian sources became dominant. These provenance changes are hypothesized to be related to the opening of the South and Equatorial Atlantic Ocean, coincident with tectonic uplift of the continental margin triggered by Africa‐Europe convergence. Finally, the difference between ɛNd(0)values of Cretaceous sediments from the Senegal continental shelf and from the deepwater basins suggests that ocean currents prevented detrital material from the Mauritanides reaching deepwater areas.
Increasing Magnitude of Hurricane Rapid Intensification in the Central and Eastern Tropical Atlantic
Authors: Balaguru Karthik , Foltz Gregory R. , Leung L. Ruby
Published: May 2018

Rapid intensification (RI) of hurricanes is notoriously difficult to predict and can contribute to severe destruction and loss of life. While past studies examined the frequency of RI occurrence, changes in RI magnitude were not considered. Here we explore changes in RI magnitude over the 30‐year satellite period of 1986–2015. In the central and eastern tropical Atlantic, which includes much of the main development region, the 95th percentile of 24‐hr intensity changes increased at 3.8 knots per decade. In the western tropical Atlantic, encompassing the Caribbean Sea and the Gulf of Mexico, trends are insignificant. Our analysis reveals that warming of the upper ocean coinciding with the positive phase of Atlantic Multidecadal Oscillation, and associated changes in the large‐scale environment, has predominantly favored RI magnitude increases in the central and eastern tropical Atlantic. These results have substantial implications for the eastern Caribbean Islands, some of which were devastated during the 2017 hurricane season.
Ablation of beta subunit of protein kinase CK2 in mouse oocytes causes follicle atresia and premature ovarian failure
Authors: Liang Qiu-Xia , Wang Zhen-Bo , Lin Fei , Zhang Chun-Hui , Sun Hong-Mei , Zhou Liang , Zhou Qian , Schatten Heide , Odile Filhol-Cochet , Brigitte Boldyreff , Sun Qing-Yuan , Qian Wei-Ping
Published: May 2018

Premature ovarian failure (POF), a major cause of female infertility, is a complex disorder, but the molecular mechanisms underlying the disorder are only poorly understood. Here we report that protein kinase CK2 contributes to maintaining follicular survival through PI3K/AKT pathway and DNA damage response pathway. Targeted deletion of CK2β in mouse oocytes from the primordial follicle stage resulted in female infertility, which was attributed to POF incurring by massive follicle atresia. Downregulated PI3K/AKT signaling was found after CK2β deletion, indicated by reduced level of phosphorylated AKT (S473, T308, and S129) and altered AKT targets related to cell survival. Further studies discovered that CK2β-deficient oocytes showed enhanced γH2AX signals, indicative of accumulative unrepaired DSBs, which activated CHK2-dependant p53 and p63 signaling. The suppressed PI3K/AKT signaling and failed DNA damage response signaling probably contribute to large-scale oocyte loss and eventually POF. Our findings provide important new clues for elucidating the mechanisms underlying follicle atresia and POF.
Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation
Authors: Zhou Qing , Eldakhakhny Sahar , Conforti Franco , Crosbie Emma J. , Melino Gerry , Sayan Berna S.
Published: May 2018

Endometrial cancer is one of the most common gynaecological cancers in developed countries. Its incidence has increased 20% over the last decade and the death rate has increased >100% over the past two decades. Current models for prediction of prognosis and treatment response are suboptimal, and as such biomarkers to support clinical decision-making and contribute to individualised treatment are needed. In this study, we show that the E3-ubiquitin ligase PIR2/RNF144B is a potential targetable biomarker in endometrial cancer. At transcript level, it is expressed both in normal endometrium and tumour samples, but at protein level, it is expressed in tumours only. By using endometrial cancer cell lines, we demonstrated that PIR2/RNF144B is stabilised via phosphorylation downstream of GSK3β and this is necessary for the proliferation of endometrial cancer cells, in the absence of oestrogenic growth stimuli. Here, inactivation of GSK3β activity is associated with loss of PIR2/RNF144B protein and consequent inhibition of cell proliferation. Our results, therefore, substantiate PIR2/RNF144B as a novel candidate for targeted therapy in endometrial cancer.
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells
Authors: Xu Dongchao , Liu Ajuan , Wang Xuan , Chen Yidan , Shen Yunyun , Tan Zhou , Qiu Mengsheng
Published: May 2018

Abstract

Glioblastoma (GBM) is the most common primary malignancy of the central nervous system (CNS) with <10% 5-year survival rate. The growth and invasion of GBM cells into normal brain make the resection and treatment difficult. A better understanding of the biology of GBM cells is crucial to the targeted therapies for the disease. In this study, we identified Septin9 (SEPT9) and Septin2 (SEPT2) as GBM-related genes through integrated multi-omics analysis across independent transcriptomic and proteomic studies. Further studies revealed that expression of SEPT9 and SEPT2 was elevated in glioma tissues and cell lines (A172, U87-MG). Knockdown of SEPT9 and SEPT2 in A172/U87-MG was able to inhibit GBM cell proliferation and arrest cell cycle progression in the S phase in a synergistic mechanism. Moreover, suppression of SEPT9 and SEPT2 decreased the GBM cell invasive capability and significantly impaired the growth of glioma xenografts in nude mice. Furthermore, the decrease in GBM cell growth caused by SEPT9 and SEPT2 RNAi appears to involve two parallel signaling pathway including the p53/p21 axis and MEK/ERK activation. Together, our integration of multi-omics analysis has revealed previously unrecognized synergistic role of SEPT9 and SEPT2 in GBM, and provided novel insights into the targeted therapy of GBM.
Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice
Authors: Wang Bin , Zhang Yingying , Dong Hongli , Gong Siyi , Wei Bin , Luo Man , Wang Hongyan , Wu Xiaohui , Liu Wei , Xu Xingshun , Zheng Yufang , Sun Miao
Published: May 2018

Tctn3 belongs to the Tectonic (Tctn) family and is a single-pass membrane protein localized at the transition zone of primary cilia as an important component of ciliopathy-related protein complexes. Previous studies showed that mutations in Tctn1 and Tctn2, two members of the tectonic family, have been reported to disrupt neural tube development in humans and mice, but the functions of Tctn3 in brain development remain elusive. In this study, Tctn3 knockout (KO) mice were generated by utilizing the piggyBac (PB) transposon system. We found that Tctn3 KO mice exhibited abnormal global development, including prenatal lethality, microphthalmia, polysyndactyly, and abnormal head, sternum, and neural tube, whereas Tctn3 heterozygous KO mice did not show abnormal development or behaviors. Further, we found that the mRNA levels of Gli1 and Ptch1, downstream signaling components of the Shh pathway, were significantly reduced. Likewise, neural tube patterning-related proteins, such as Shh, Foxa2, and Nkx2.2, were altered in their distribution. Interestingly, Tctn3 KO led to significant changes in apoptosis-related proteins, including Bcl-2, Bax, and cleaved PARP1, resulting in reduced numbers of neuronal cells in embryonic brains. Tctn3 KO inhibited the PI3K/Akt signaling pathway but not the mTOR-dependent pathway. The small molecule SC79, a specific Akt activator, blocked apoptotic cell death in primary mouse embryonic fibroblasts from Tctn3 KO mice. Finally, NPHP1, a protein with anti-apoptotic ability, was found to form a complex with Tctn3, and its levels were decreased in Tctn3 KO mice. In conclusion, our results show that Tctn3 KO disrupts the Shh signaling pathway and neural tube patterning, resulting in abnormal embryonic development, cellular apoptosis, and prenatal death in mice.
78,000-year-old record of Middle and Later Stone Age innovation in an East African tropical forest
Authors: Shipton Ceri , Roberts Patrick , Archer Will , Armitage Simon J. , Bita Caesar , Blinkhorn James , Courtney-Mustaphi Colin , Crowther Alison , Curtis Richard , Errico Francesco d’ , Douka Katerina , Faulkner Patrick , Groucutt Huw S. , Helm Richard , Herries Andy I. R , Jembe Severinus , Kourampas Nikos , Lee-Thorp Julia , Marchant Rob , Mercader Julio , Marti Africa Pitarch , Prendergast Mary E. , Rowson Ben , Tengeza Amini , Tibesasa Ruth , White Tom S. , Petraglia Michael D. , Boivin Nicole
Published: May 2018

The Middle to Later Stone Age transition in Africa has been debated as a significant shift in human technological, cultural, and cognitive evolution. However, the majority of research on this transition is currently focused on southern Africa due to a lack of long-term, stratified sites across much of the African continent. Here, we report a 78,000-year-long archeological record from Panga ya Saidi, a cave in the humid coastal forest of Kenya. Following a shift in toolkits ~67,000 years ago, novel symbolic and technological behaviors assemble in a non-unilinear manner. Against a backdrop of a persistent tropical forest-grassland ecotone, localized innovations better characterize the Late Pleistocene of this part of East Africa than alternative emphases on dramatic revolutions or migrations.
Gravitational clustering of cosmic relic neutrinos in the Milky Way
Authors: Zhang Jue , Zhang Xin
Published: May 2018

The standard model of cosmology predicts the existence of cosmic neutrino background in the present Universe. To detect cosmic relic neutrinos in the vicinity of the Earth, it is necessary to evaluate the gravitational clustering effects on relic neutrinos in the Milky Way. Here we introduce a reweighting technique in the N-one-body simulation method, so that a single simulation can yield neutrino density profiles for different neutrino masses and phase space distributions. In light of current experimental results that favor small neutrino masses, the neutrino number density contrast around the Earth is found to be almost proportional to the square of neutrino mass. The density contrast-mass relation and the reweighting technique are useful for studying the phenomenology associated with the future detection of the cosmic neutrino background.
Publisher Correction: RING tetramerization is required for nuclear body biogenesis and PML sumoylation
Authors: Wang Pengran , Benhenda Shirine , Wu Haiyan , Lallemand-Breitenbach Valérie , Zhen Tao , Jollivet Florence , Peres Laurent , Li Yuwen , Chen Sai-Juan , Chen Zhu , de Thé Hugues , Meng Guoyu
Published: May 2018

In the originally published version of this Article, the authors Sai-Juan Chen and Zhu Chen were incorrectly listed as being affiliated with ‘University Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR7212, Equipe labellisée LNCC, Hôpital St. Louis 1, Paris 75475, France’, and the affiliation ‘Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China’ was inadvertently omitted. These errors have now been corrected in both the PDF and HTML versions of the Article.
Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
Authors: Ostrom Quinn T. , Kinnersley Ben , Wrensch Margaret R. , Eckel-Passow Jeanette E. , Armstrong Georgina , Rice Terri , Chen Yanwen , Wiencke John K. , McCoy Lucie S. , Hansen Helen M. , Amos Christopher I. , Bernstein Jonine L. , Claus Elizabeth B. , Il’yasova Dora , Johansen Christoffer , Lachance Daniel H. , Lai Rose K. , Merrell Ryan T. , Olson Sara H. , Sadetzki Siegal , Schildkraut Joellen M. , Shete Sanjay , Rubin Joshua B. , Lathia Justin D. , Berens Michael E. , Andersson Ulrika , Rajaraman Preetha , Chanock Stephen J. , Linet Martha S. , Wang Zhaoming , Yeager Meredith ,   GliomaScan consortium, Beane Freeman Laura E. , Koutros Stella , Albanes Demetrius , Visvanathan Kala , Stevens Victoria L. , Henriksson Roger , Michaud Dominique S. , Feychting Maria , Ahlbom Anders , Giles Graham G. , Milne Roger , McKean-Cowdin Roberta , Le Marchand Loic , Stampfer Meir , Ruder Avima M. , Carreon Tania , Hallmans Göran , Zeleniuch-Jacquotte Anne , Gaziano J. Michael , Sesso Howard D. , Purdue Mark P. , White Emily , Peters Ulrike , Buring Julie , Houlston Richard S. , Jenkins Robert B. , Melin Beatrice , Bondy Melissa L. , Barnholtz-Sloan Jill. S.
Published: May 2018

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
Author Correction: Potential damaging mutation in LRP5 from genome sequencing of the first reported chimpanzee with the Chiari malformation
Authors: Solis-Moruno Manuel , de Manuel Marc , Hernandez-Rodriguez Jessica , Fontsere Claudia , Gomara-Castaño Alba , Valsera-Naranjo Cristina , Crailsheim Dietmar , Navarro Arcadi , Llorente Miquel , Riera Laura , Feliu-Olleta Olga , Marques-Bonet Tomas
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Trafficking, localization and degradation of the Na+,HCO3− co-transporter NBCn1 in kidney and breast epithelial cells
Authors: Olesen Christina Wilkens , Vogensen Jens , Axholm Ida , Severin Marc , Schnipper Julie , Pedersen Isabella Skandorff , von Stemann Jakob Hjorth , Schrøder Jacob Morville , Christensen Dan Ploug , Pedersen Stine Falsig
Published: May 2018

The Na+;HCO3− co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL). Glutathione-S-Transferase-pulldown of the C-tail followed by mass spectrometry analysis revealed putative interactions with multiple sorting-, degradation- and retention factors, including the scaffolding protein RACK1. Pulldown of FLAG-tagged deletion constructs mapped the RACK1 interaction to the proximal NBCn1 C-tail. Proximity Ligation Assay and co-immunoprecipitation confirmed that native NBCn1 interacts with RACK1 in a cellular context. Consistent with a functional role of this complex, RACK1 knockdown reduced NBCn1 membrane localization without affecting total NBCn1 expression. Notably, only non-confluent cells exhibited detectable NBCn1-RACK1 plasma membrane co-localization, suggesting that RACK1 regulates the trafficking of NBCn1 to the membrane. Whereas total NBCn1 degradation was slow, with a half-life of more than 24 h, one-third of surface NBCn1 was constitutively endocytosed from the basolateral membrane within 60 min. This suggests that a fraction of NBCn1 exhibits recycling between the basolateral membrane and intracellular compartment(s). Our findings have important implications for understanding NBCn1 regulation as well as its dysregulation in disease.
Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys
Authors: Slomka Marek J. , Seekings Amanda H. , Mahmood Sahar , Thomas Saumya , Puranik Anita , Watson Samantha , Byrne Alexander M. P. , Hicks Daniel , Nunez Alejandro , Brown Ian H. , Brookes Sharon M.
Published: May 2018

The China-origin H7N9 low pathogenicity avian influenza virus (LPAIV) emerged as a zoonotic threat in 2013 where it continues to circulate in live poultry markets. Absence of overt clinical signs in poultry is a typical LPAIV infection outcome, and has contributed to its insidious maintenance in China. This study is the first description of H7N9 LPAIV (A/Anhui/1/13) infection in turkeys, with efficient transmission to two additional rounds of introduced contact turkeys which all became infected during cohousing. Surprisingly, mortality was observed in six of eight (75%) second-round contact turkeys which is unusual for LPAIV infection, with unexpected systemic dissemination to many organs beyond the respiratory and enteric tracts, but interestingly no accompanying mutation to highly pathogenic AIV. The intravenous pathogenicity index score for a turkey-derived isolate (0.39) affirmed the LPAIV phenotype. However, the amino acid change L235Q in the haemagglutinin gene occurred in directly-infected turkeys and transmitted to the contacts, including those that died and the two which resolved infection to survive to the end of the study. This polymorphism was indicative of a reversion from mammalian to avian adaptation for the H7N9 virus. This study underlined a new risk to poultry in the event of H7N9 spread beyond China.
Salivary levels of total huntingtin are elevated in Huntington’s disease patients
Authors: Corey-Bloom Jody , Haque Ameera S. , Park Sungmee , Nathan Ajay S. , Baker Robert W. , Thomas Elizabeth A.
Published: May 2018

Patients with Huntington’s disease (HD), an autosomal-dominant neurodegenerative disease, show substantial variability in age-of-onset, symptom severity and course of illness, warranting the need for biomarkers to anticipate and monitor these features. The HD gene encodes the disease protein huntingtin (Htt), a potentially useful biomarker for this disease. In the current study, we determined whether total Htt protein (normal plus mutant; “tHtt”) could be reliably measured in human saliva, a body fluid that is much more accessible compared to cerebral spinal fluid or even blood, and whether salivary levels of tHtt were clinically meaningful. We collected 146 saliva samples from manifest HD patients, early-premanifest individuals, late-premanifest patients, gene-negative family members and normal controls. We found that tHtt protein could be reliably and stably detected in human saliva and that tHtt levels were significantly increased in saliva from HD individuals compared to normal controls. Salivary tHtt showed no gender effects, nor were levels correlated with total protein levels in saliva. Salivary tHtt was significantly positively correlated with age, but not age-of-onset or CAG-repeat length. Importantly, salivary tHtt was significantly correlated with several clinical measures, indicating relevance to disease symptom onset and/or severity. Measurements of salivary tHtt offer significant promise as a relevant, non-invasive disease biomarker for HD, and its use could be implemented into clinical applications.
Publisher Correction: Impact of remotely generated eddies on plume dispersion at abyssal mining sites in the Pacific
Authors: Aleynik Dmitry , Inall Mark E. , Dale Andrew , Vink Annemiek
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Three-dimensional hot electron photovoltaic device with vertically aligned TiO2 nanotubes
Authors: Goddeti Kalyan C. , Lee Changhwan , Lee Young Keun , Park Jeong Young
Published: May 2018

Titanium dioxide (TiO2) nanotubes with vertically aligned array structures show substantial advantages in solar cells as an electron transport material that offers a large surface area where charges travel linearly along the nanotubes. Integrating this one-dimensional semiconductor material with plasmonic metals to create a three-dimensional plasmonic nanodiode can influence solar energy conversion by utilizing the generated hot electrons. Here, we devised plasmonic Au/TiO2 and Ag/TiO2 nanodiode architectures composed of TiO2 nanotube arrays for enhanced photon absorption, and for the subsequent generation and capture of hot carriers. The photocurrents and incident photon to current conversion efficiencies (IPCE) were obtained as a function of photon energy for hot electron detection. We observed enhanced photocurrents and IPCE using the Ag/TiO2 nanodiode. The strong plasmonic peaks of the Au and Ag from the IPCE clearly indicate an enhancement of the hot electron flux resulting from the presence of surface plasmons. The calculated electric fields and the corresponding absorbances of the nanodiode using finite-difference time-domain simulation methods are also in good agreement with the experimental results. These results show a unique strategy of combining a hot electron photovoltaic device with a three-dimensional architecture, which has the clear advantages of maximizing light absorption and a metal–semiconductor interface area.
Amino acid compositions contribute to the proteins’ evolution under the influence of their abundances and genomic GC content
Authors: Du Meng-Ze , Liu Shuo , Zeng Zhi , Alemayehu Labena Abraham , Wei Wen , Guo Feng-Biao
Published: May 2018

Inconsistent results on the association between evolutionary rates and amino acid composition of proteins have been reported in eukaryotes. However, there are few studies of how amino acid composition can influence evolutionary rates in bacteria. Thus, we constructed linear regression models between composition frequencies of amino acids and evolutionary rates for bacteria. Compositions of all amino acids can on average explain 21.5% of the variation in evolutionary rates among 273 investigated bacterial organisms. In five model organisms, amino acid composition contributes more to variation in evolutionary rates than protein abundance, and frequency of optimal codons. The contribution of individual amino acid composition to evolutionary rate varies among organisms. The closer the GC-content of genome to its maximum or minimum, the better the correlation between the amino acid content and the evolutionary rate of proteins would appear in that genome. The types of amino acids that significantly contribute to evolutionary rates can be grouped into GC-rich and AT-rich amino acids. Besides, the amino acid with high composition also contributes more to evolutionary rates than amino acid with low composition in proteome. In summary, amino acid composition significantly contributes to the rate of evolution in bacterial organisms and this in turn is impacted by GC-content.