bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
Authors: Dajani Rana , Li Jin , Wei Zhi , March Michael E. , Xia Qianghua , Khader Yousef , Hakooz Nancy , Fatahallah Raja , El-Khateeb Mohammed , Arafat Ala , Saleh Tareq , Dajani Abdel Rahman , Al-Abbadi Zaid , Abdul Qader Mohamed , Shiyab Abdel Halim , Bateiha Anwar , Ajlouni Kamel , Hakonarson Hakon
Published: August 2017

The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10−8) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10−5) and it is a robust eQTL for the gene, MLXIP (P = 1.10 × 10−14), and is significantly associated with methylation level in MLXIP, the functions of which involves cellular glucose response. Therefore, in this first GWAS of T2D in Jordan subpopulations, we identified novel and unique susceptibility loci which may help inform the genetic underpinnings of T2D in other populations.
Quercivorol as a lure for the polyphagous and Kuroshio shot hole borers, Euwallacea spp. nr. fornicatus (Coleoptera: Scolytinae), vectors of Fusarium dieback
Authors: Dodge Christine , Coolidge Jessica , Cooperband Miriam , Cossé Allard , Carrillo Daniel , Stouthamer Richard
Published: August 2017

The polyphagous shot hole borer and Kuroshio shot hole borer, two members of the Euwallacea fornicatus species complex (Coleoptera: Curculionidae: Scolytinae), are invasive ambrosia beetles that harbor distinct species of Fusarium fungal symbionts. Together with the damage caused by gallery construction, these two phytopathogenic Fusarium species are responsible for the emerging tree disease Fusarium dieback, which affects over 50 common tree species in Southern California. Host trees suffer branch dieback as the xylem is blocked by invading beetles and fungi, forcing the costly removal of dead and dying trees in urban areas. The beetles are also threatening natural riparian habitats, and avocado is susceptible to Fusarium dieback as well, resulting in damage to the avocado industries in California and Israel. Currently there are no adequate control mechanisms for shot hole borers. This paper summarizes efforts to find a suitable lure to monitor shot hole borer invasions and dispersal. Field trials were conducted in two counties in Southern California over a span of two years. We find that the chemical quercivorol is highly attractive to these beetles, and perform subsequent field experiments attempting to optimize this lure. We also explore other methods of increasing trap catch and effects of other potential attractants, as well as the deterrents verbenone and piperitone.
Late Pleistocene songbirds of Liang Bua (Flores, Indonesia); the first fossil passerine fauna described from Wallacea
Authors: Meijer Hanneke J.M. , Awe Due Rokus , Sutikna Thomas , Saptomo Wahyu , Jatmiko  , Wasisto Sri , Tocheri Matthew W. , Mayr Gerald
Published: August 2017

Background

Passerines (Aves: Passeriformes) dominate modern terrestrial bird communities yet their fossil record is limited. Liang Bua is a large cave on the Indonesian island of Flores that preserves Late Pleistocene–Holocene deposits (∼190 ka to present day). Birds are the most diverse faunal group at Liang Bua and are present throughout the stratigraphic sequence.

Methods

We examined avian remains from the Late Pleistocene deposits of Sector XII, a 2 × 2 m area excavated to about 8.5 m depth. Although postcranial passerine remains are typically challenging to identify, we found several humeral characters particularly useful in discriminating between groups, and identified 89 skeletal elements of passerines.

Results

At least eight species from eight families are represented, including the Large-billed Crow (Corvuscf.macrorhynchos),the Australasian Bushlark (Mirafra javanica),a friarbird (Philemonsp.), and the Pechora Pipit (Anthuscf.gustavi).

Discussion

These remains constitute the first sample of fossil passerines described in Wallacea. Two of the taxa no longer occur on Flores today; a large sturnid (cf.Acridotheres) and a grassbird (Megalurussp.). Palaeoecologically, the songbird assemblage suggests open grassland and tall forests, which is consistent with conditions inferred from the non-passerine fauna at the site.Corvuscf.macrorhynchos, found in theHomo floresiensis-bearing layers, was likely part of a scavenging guild that fed on carcasses ofStegodon florensis insularisalongside vultures (Trigonocepssp.), giant storks (Leptoptilos robustus), komodo dragons (Varanus komodoensis), and probablyH. floresiensisas well.
Are coastal resources of NW Portugal fingerprinting hydrocarbons released from the Prestige accident?
Authors: Ferreira AM , Micaelo C , Vale C
Published: August 2017

Seventy-one samples of mussels, sardine, hake, blue whiting and pouting from the NW Portuguese coast, collected between 18 November 2002 and 6 January 2003, were analyzed for total hydrocarbons, individual n-alkanes and major isoprenoids, pristane and phytane. Hydrocarbons (expressed on chrysene equivalents) registered in whole soft tissues of mussels were below 0.5 µg g–1, with a few exceptions (maximum 1.6 µg g–1). Relatively low levels and sporadic enhanced values were also found in fish fillet samples. In spite of this, analyses of individual n-alkanes and major isoprenoids showed that 10–61% of the samples (according to the species) exhibited these compounds in the proportions of the Prestige fuel signature. Similar diagnostic ratios in biological samples and Prestige fuel and n-alkane composition corroborate the fingerprint hypothesis in coastal resources from NW Portugal.
Formation of the thermohaline structure of water in the Bahía de La Paz from summer to autumn
Authors: González-Salinas F , Zaytsev O , Makarov V
Published: August 2017

The summer-autumn formation of the thermohaline structure of the coastal deepwater body was studied in Bahía de La Paz, Gulf of California, from measurements the thermohaline variables taken in October 1997, November 1998, August 1999, and in an adjacent area of the Gulf of California in July 1997. In August 1999, intense density stratification was recorded from the surface to 60-m depth, because of a positive daily heat balance and weak vertical mixing. In autumn (Oct. 1997 and Nov. 1998), the upper mixed layer (ML) was 40–50-m thick, and the thermocline had a maximum vertical gradient up to 0.6ºC per meter. The three-dimensional distribution of density shows concave isopycnics towards the center of the bay, suggesting the possible existence of anticyclonic vorticity. The non-uniformity of this spatial mass field was formed by local heating and evaporation processes, and by the water exchange with the open ocean through the mouths of the bay. The physical reasons for the variations in the ML are discussed. The deepwater body (>150 m) maintained almost constant thermohaline variables during the study and no noticeable variations were detected in the surface layer. The T-S diagrams were different from those of the Gulf of California water mass and similar to Subtropical Subsurface waters ones (less saline). In October 1997, a 2.5ºC increase in temperature was measured at the surface layer which considered related to the peak of the 1997 El Niño.
Geographic variability of the concentration of Hg, Co, Fe and Ni in mussels Mytilus californianus (Conrad, 1837) from the coast of Baja California
Authors: Gutiérrez-Galindo EA , Muñoz-Barbosa A
Published: August 2017

The spatial distribution of the Hg, Fe, Co, and Ni pollution was determined in the Northwest coast of Baja California using the mussel Mytilus californianus as biomonitor. Samplings of mussels were done during February and July 1994 at eight sites located along 300 km of coast, from Punta Bandera (10 km south of the Mexico-USA border) to San Quintin (300 km south of the border). The spatial distribution of Hg showed a North-South gradient from Punta Bandera (0.331 µg g–1) to San Quintin (0.094 µg g–1). This gradient suggests that the Hg distribution is affected by anthropogenic activities nearby the Mexico-USA border. Cobalt showed a spatial distribution with significantly higher concentrations (P < 0.01) in Piedra Blanca (2.98 µg g–1) and San Quintin (2.26 µg g–1). Nickel showed an irregular spatial distribution with higher concentrations in Punta Bandera (2.07 µg g–1) and San Quintin (1.83 µg g–1). In general, Fe showed higher concentrations from Punta Bandera to Bajamar in February (515–504 µg g–1); except for Punta China (1142 µg g–1) that is characterized by the extraction of petrous material for the cement industry, the sampling sites in the central part of the study area showed lower concentrations. No significant correlations were observed among metals and the biological variables of the analyzed mussels. The cluster analysis among metals, grouped Hg with elements (Ag and Pb) associated with anthropogenic activities in a previous study. Cluster analysis showed three geographical zones that could be defined as polluted, transition and clean zone, respectively.
Tat transport in Escherichia coli requires zwitterionic phosphatidylethanolamine but no specific negatively charged phospholipid
Authors: Rathmann Claudia , Schlösser Amelie S. , Schiller Jürgen , Bogdanov Mikhail , Brüser Thomas
Published: August 2017

Translocation of folded proteins by the Tat system of Escherichia coli is believed to rely on the presence of phosphatidylethanolamine (PE) and the negatively charged phospholipids cardiolipin (CL) and phosphatidylglycerol (PG). Here, we show that while PE is indeed essential for activity, the Tat system is fully functional in a clsA/clsB/clsC deletion strain lacking CL, and in a pgsA deletion strain lacking both PG and CL during aerobic growth on complex media. In contrast to early studies that relied on strains with reduced lipid levels, this study therefore demonstrates that PG and CL are dispensable for Tat transport. The lack of these lipids may be compensated by other anionic phospholipids such as phosphatidic acid, CDP‐diacylglycerol or N‐acyl‐PE.
Pulse‐like partial ruptures and high‐frequency radiation at creeping‐locked transition during megathrust earthquakes
Authors: Michel Sylvain , Avouac Jean‐Philippe , Lapusta Nadia , Jiang Junle
Published: August 2017

Megathrust earthquakes tend to be confined to fault areas locked in the interseismic period and often rupture them only partially. For example, during the 2015 M7.8 Gorkha earthquake, Nepal, a slip pulse propagating along strike unzipped the bottom edge of the locked portion of the Main Himalayan Thrust (MHT). The lower edge of the rupture produced dominant high‐frequency (>1 Hz) radiation of seismic waves. We show that similar partial ruptures occur spontaneously in a simple dynamic model of earthquake sequences. The fault is governed by standard laboratory‐based rate‐and‐state friction with the aging law and contains one homogenous velocity‐weakening (VW) region embedded in a velocity‐strengthening (VS) area. Our simulations incorporate inertial wave‐mediated effects during seismic ruptures (they are thus fully dynamic) and account for all phases of the seismic cycle in a self‐consistent way. Earthquakes nucleate at the edge of the VW area and partial ruptures tend to stay confined within this zone of higher prestress, producing pulse‐like ruptures that propagate along strike. The amplitude of the high‐frequency sources is enhanced in the zone of higher, heterogeneous stress at the edge of the VW area.
Connecting tropical climate change with Southern Ocean heat uptake
Authors: Hwang Yen‐Ting , Xie Shang‐Ping , Deser Clara , Kang Sarah M.
Published: August 2017

Under increasing greenhouse gas forcing, climate models project tropical warming that is greater in the Northern than the Southern Hemisphere, accompanied by a reduction in the northeast trade winds and a strengthening of the southeast trades. While the ocean‐atmosphere coupling indicates a positive feedback, what triggers the coupled asymmetry and favors greater warming in the northern tropics remains unclear. Far away from the tropics, the Southern Ocean (SO) has been identified as the major region of ocean heat uptake. Beyond its local effect on the magnitude of sea surface warming, we show by idealized modeling experiments in a coupled slab ocean configuration that enhanced SO heat uptake has a profound global impact. This SO‐to‐tropics connection is consistent with southward atmospheric energy transport across the equator. Enhanced SO heat uptake results in a zonally asymmetric La‐Nina‐like pattern of sea surface temperature change that not only affects tropical precipitation but also has influences on the Asian and North American monsoons.
An abridged history of federal involvement in space weather forecasting
Authors: Caldwell Becaja , McCarron Eoin , Jonas Seth
Published: August 2017

Public awareness of space weather and its adverse effects on critical infrastructure systems, services, and technologies (e.g., the electric grid, telecommunications, and satellites) has grown through recent media coverage and scientific research. However, federal interest and involvement in space weather dates back to the decades between World War I and World War II when the National Bureau of Standards led efforts to observe, forecast, and provide warnings of space weather events that could interfere with high‐frequency radio transmissions. The efforts to observe and predict space weather continued through the 1960s during the rise of the Cold War and into the present with U.S. government efforts to prepare the nation for space weather events. This paper provides a brief overview of the history of federal involvement in space weather forecasting from World War II, through the Apollo Program, and into the present.
Calibration of the GOES 13/15 high‐energy proton detectors based on the PAMELA solar energetic particle observations
Authors: Bruno A.
Published: August 2017

The Energetic Proton, Electron, and Alpha Detector (EPEAD) and High Energy Proton and Alpha Detector (HEPAD) instruments on the Geostationary Operational Environmental Satellite (GOES) spacecraft have served over many years as monitors of the solar particle intensities, surveying the Sun and measuring in situ its effect on the near‐Earth solar‐terrestrial environment. However, the reconstruction of the differential energy spectra is affected by large uncertainties related to the poor energy resolution, the small geometrical factor, and the high contamination by out‐of‐acceptance particles. In this work, the high‐quality data set from the Payload for Antimatter Matter Exploration and Light‐nuclei Astrophysics (PAMELA) space mission is used to calibrate the high‐energy (>80 MeV) proton channels of the EPEAD and the HEPAD sensors on board the GOES 13 and 15, bringing the measured spectral intensities inline with those registered by PAMELA. Suggested corrections significantly reduce the uncertainties on the response of GOES detectors, thus improving the reliability of the spectroscopic observations of solar energetic particle events.
The Stl repressor from Staphylococcus aureus is an efficient inhibitor of the eukaryotic fruitfly dUTPase
Authors: Benedek András , Pölöskei István , Ozohanics Olivér , Vékey Károly , Vértessy Beáta G.
Published: August 2017

DNA metabolism and repair is vital for the maintenance of genome integrity. Specific proteinaceous inhibitors of key factors in this process have high potential for deciphering pathways of DNA metabolism and repair. The dUTPase enzyme family is responsible for guarding against erroneous uracil incorporation into DNA. Here, we investigate whether the staphylococcal Stl repressor may interact with not only bacterial but also eukaryotic dUTPase. We provide experimental evidence for the formation of a strong complex between Stl and Drosophila melanogasterdUTPase. We also find that dUTPase activity is strongly diminished in this complex. Our results suggest that the dUTPase protein sequences involved in binding to Stl are at least partially conserved through evolution from bacteria to eukaryotes.
H
alobacteriales
Authors: Oren Aharon , Ventosa Antonio , Kamekura Masahiro
Published: August 2017

Ha.lo.bac.te.ri.a'les. N.L. neut. n.
Halobacterium
the type genus of the order; −
ales
ending to denote an order; N.L. fem. pl. n.
Halobacteriales
the order of
Halobacterium
.

Euryarchaeota / Halobacteria / Halobacteriales

The order
Halobacteriales
, belonging to the class
Halobacteria
, consists of three families: the
Halobacteriaceae
, the
Haloarculaceae
, and the
Halococcaceae
. All members of the family are neutrophilic or alkaliphilic, extremely halophilic Archaea, mostly red‐pink pigmented and generally leading an aerobic life style. Based on the phylogenomic analyses, the orders
Haloferacales
and
Natrialbales
were separated from the
Halobacteriales
in 2015.
Empathy's Relation to Appraisal of the Emotional Child Witness
Authors: Bederian‐Gardner Daniel , Goldfarb Deborah , Goodman Gail S.
Published: August 2017

When observing others, we often try to determine how they ‘really feel’ deep down inside (emotional feeling) regardless of their outward expression (emotional appearance). We examined whether child victim empathy predicts appraisal of a child sexual assault victim's emotional feelings and, in turn, child and defendant believability and verdict decisions. Undergraduates (N = 50) rated photographs of 5‐ and 13‐year‐olds' degree of sadness. Then, a new group of undergraduates (N = 354), randomly assigned within a 2 (victim age) × 2 (victim gender) × 3 (victim sadness: low, medium, and high/teary) factorial design, read trial scenarios accompanied by one of the photographs. Participants rated the victim's emotional feeling and emotional appearance, victim and defendant believability, defendant guilt, and confidence in their verdict. A structural equation model that included a relation between empathy and emotion appraisal fit the data well: Empathy predicted appraisal of the victim's feelings, which, in turn, predicted perceived believability. Implications are discussed.Copyright © 2017 John Wiley & Sons, Ltd.
Colorimetric Nanofibers as Optical Sensors
Authors: Schoolaert Ella , Hoogenboom Richard , De Clerck Karen
Published: August 2017

Sensors play a major role in many applications today, ranging from biomedicine to safety equipment, where they detect and warn us about changes in the environment. Nanofibers, characterized by high porosity, flexibility, and a large specific surface area, are the ideal material for ultrasensitive, fast‐responding, and user‐friendly sensor design. Indeed, a large specific surface area increases the sensitivity and response time of the sensor as the contact area with the analyte is enlarged. Thanks to the flexibility of membranes, nanofibrous sensors cannot only be applied in high‐end analyte detection, but also in personal, daily use. Many different nanofibrous sensors have already been designed; albeit, the most straightforward and easiest‐to‐interpret sensor response is a visual change in color, which is of particular interest in the case of warning signals. Recently, many researchers have focused on the design of so‐called colorimetric nanofibers, which typically involve the incorporation of a colorimetric functionality into the nanofibrous matrix. Many different strategies have been used and explored for colorimetric nanofibrous sensor design, which are outlined in this feature article. The many examples and applications demonstrate the value of colorimetric nanofibers for advanced optical sensor design, and could provide directions for future research in this area.
Molybdenum Oxides – From Fundamentals to Functionality
Authors: de Castro Isabela Alves , Datta Robi Shankar , Ou Jian Zhen , Castellanos‐Gomez Andres , Sriram Sharath , Daeneke Torben , Kalantar‐zadeh Kourosh
Published: August 2017

The properties and applications of molybdenum oxides are reviewed in depth. Molybdenum is found in various oxide stoichiometries, which have been employed for different high‐value research and commercial applications. The great chemical and physical characteristics of molybdenum oxides make them versatile and highly tunable for incorporation in optical, electronic, catalytic, bio, and energy systems. Variations in the oxidation states allow manipulation of the crystal structure, morphology, oxygen vacancies, and dopants, to control and engineer electronic states. Despite this overwhelming functionality and potential, a definitive resource on molybdenum oxide is still unavailable. The aim here is to provide such a resource, while presenting an insightful outlook into future prospective applications for molybdenum oxides.
Large‐Scale Synthesis of Freestanding Layer‐Structured PbI2 and MAPbI3 Nanosheets for High‐Performance Photodetection
Authors: Lan Changyong , Dong Ruoting , Zhou Ziyao , Shu Lei , Li Dapan , Yip SenPo , Ho Johnny C.
Published: August 2017

Recently, due to the possibility of thinning down to the atomic thickness to achieve exotic properties, layered materials have attracted extensive research attention. In particular, PbI2, a kind of layered material, and its perovskite derivatives, CH3NH3PbI3 (i.e., MAPbI3), have demonstrated impressive photoresponsivities for efficient photodetection. Herein, the synthesis of large‐scale, high‐density, and freestanding PbI2 nanosheets is demonstrated by manipulating the microenvironment during physical vapor deposition. In contrast to conventional two‐dimensional (2D) growth along the substrate surface, the essence here is the effective nucleation of microplanes with different angles relative to the in‐plane direction of underlying rough‐surfaced substrates. When configured into photodetectors, the fabricated device exhibits a photoresponsivity of 410 mA W−1, a detectivity of 3.1 × 1011 Jones, and a fast response with the rise and decay time constants of 86 and 150 ms, respectively, under a wavelength of 405 nm. These PbI2 nanosheets can also be completely converted into MAPbI3 materials via chemical vapor deposition with an improved photoresponsivity up to 40 A W−1. All these performance parameters are comparable to those of state‐of‐the‐art layered‐material‐based photodetectors, revealing the technological potency of these freestanding nanosheets for next‐generation high‐performance optoelectronics.
Palladium‐Catalyzed Synthesis of N‐Cyclohexyl Anilines from Phenols with Hydrazine or Hydroxylamine via N‐N/O Cleavage
Authors: Li Jiang‐Sheng , Qiu Zihang , Li Chao‐Jun
Published: August 2017

Direct access to amines from biomass‐based phenols via deoxygenative transformation remains greatly challenging in organic synthesis. Herein, we present a palladium‐catalyzed deoxygenative amination of phenols (and their benzyl ether) with hydrazine as nitrogen source. The hydroxylamine/formic acid can be substituted for hydrazine in some cases. This deoxyamination features the involvement of a complex C−O bond and N−N/O bond‐cleavage process and allows for the construction of N‐substituted cyclohexyl anilines from an array of phenols by finely controlling the reaction conditions in moderate to good yields.

magnified image
Monoclinic (K,Na)NbO3 Ferroelectric Phase in Epitaxial Films
Authors: Luo Jin , Sun Wei , Zhou Zhen , Lee Hyun‐Young , Wang Ke , Zhu Fangyuan , Bai Yu , Wang Zhan Jie , Li Jing‐Feng
Published: August 2017

Monoclinic phases, as intermediate phases at the morphotropic phase boundary, have been considered as the origin of high piezoelectricity in various piezoelectric systems. However, those monoclinic phases have seldom been experimentally observed at the phase boundary in lead‐free (K,Na)NbO3 (KNN)‐based materials. This work shows that KNN epitaxial thin films demonstrate a monoclinic MC phase stabilized by elastic strain at room temperature, which is identified by both synchrotron X‐ray reciprocal space mapping and piezoresponse force microscopy. It is revealed that the piezoelectricity is greatly enhanced at 170 °C due to the monoclinic MC–MA phase boundary. The discovery of monoclinic phases in this work may open an avenue for developing a new thermotropic phase boundary in KNN‐based materials. The results also provide a guide for the exploration of high piezoelectricity driven by monoclinic phases in lead‐free piezoelectric materials.
An Analytical Modeling of Field Electron Emission for a Vertical Wedged Ordered Nanostructure
Authors: Shen Yan , Xu Ningsheng , Ye Peng , Zhang Yu , Liu Fei , Chen Jun , She Juncong , Deng Shaozhi
Published: August 2017

The development of field electron emission materials requires purposeful analytical modeling of structural features. A vertical wedged ordered nanostructure shows better field emission current density because of its in‐plane continuity at the top emission edge: Individually, its calculated average current density can be 8.3–26.7 times larger than a tapered nanostructure when its bottom area s increases from 0.5 to 2.5 µm2, can be 2.2–12.7 times as its radius of top curvature r decreases from 65 to 5 nm, and can be 7.3–17.3 times as its length L increases from 0.5 to 5 µm. For an ordered nanostructure array, its average current density can be about 160 times larger than the a reference tapered array when the individual elements are closely aligned. Over three orders of magnitude improvment can be observed when optimal emitter spacing conditions are used. Structural analytical models and numerical simulation prove to be in good correspondence with previously reported experimental data, and may serve as a guide for the design and preparation of field electron emission materials with a clear purpose in the future.
Network Analysis in Community Psychology: Looking Back, Looking Forward
Authors: Neal Zachary P. , Neal Jennifer Watling
Published: August 2017

Highlights

Network analysis is ideally suited for community psychology research because it focuses on context.

Use of network analysis in community psychology is growing.

Network analysis in community psychology has employed some potentially problematic practices.

Recommended practices are identified to improve network analysis in community psychology.
No change in energy efficiency in lactation: Insights from a longitudinal study
Authors: Bender Richard L. , Williams Heather S. , Dufour Darna L.
Published: August 2017

Objectives

Lactation is the most energy‐demanding phase of reproduction for human females, but it is still unclear how women in different environments are able to meet this additional energy demand. Previous studies have investigated whether changes in metabolism could have an energy‐sparing effect in lactation, with conflicting results. Here, we asked whether increased energy efficiency in physical activity serves as an energy‐sparing mechanism in lactation.

Methods

We used a longitudinal design with a control group. Participants were 33 well‐nourished, exclusively breastfeeding women and 29 non‐pregnant, non‐lactating (NPNL) controls aged 32 ± 4 years. Lactating women were measured at peak‐ and post‐lactation. NPNL controls completed a baseline measurement and a follow‐up visit. Energy efficiency in physical activity was assessed using a graded submaximal exercise test and calculated as delta efficiency (change in work accomplished over change in energy expended) and gross efficiency (work accomplished over energy expended).

Results

There was no significant change in either delta efficiency or gross efficiency from peak to post lactation in lactating women, and no significant difference in delta efficiency between lactating women and NPNL controls at any time period. However, lactating women showed greater between‐visit variation in delta efficiency than the NPNL controls. Additionally, 79% of lactating participants lost weight between visits (mean weight loss −3.6 ± 2.3kg), consistent with a mobilization of body tissues to support lactation.

Conclusion

We found no support for the idea that lactating women undergo an increase in energy efficiency to support the energy costs of lactation.
The pregnancy in neurofibromatosis 1: A retrospective register‐based total population study
Authors: Leppävirta Jussi , Kallionpää Roope A. , Uusitalo Elina , Vahlberg Tero , Pöyhönen Minna , Timonen Susanna , Peltonen Juha , Peltonen Sirkku
Published: August 2017

The objective of this retrospective total population study was to form a view of the pregnancies of the patients with neurofibromatosis type 1 (NF1). A cohort of 1,410 Finnish patients with NF1 was acquired by searching NF1‐related inpatient and outpatient hospital visits and confirming the diagnoses by reviewing the medical records. Ten matched control persons per patient with NF1 were collected from Population Register Centre. Study persons were linked to data from Medical Birth Register and Care Register for Health Care through the personal identity code. Cesarean deliveries, hypertension/preeclampsia, and placental abruptions were more common among mothers with NF1 with adjusted odds ratios of 2.24 (95%CI 1.63–3.07), 1.96 (95%CI 1.18–3.24), and 13.40 (95%CI 4.26–42.13), respectively. The adjusted mean pregnancy duration was 0.65 (95%CI 0.42–0.88) weeks shorter among the mothers with NF1 than in the control group consisting of non‐NF1 mothers giving birth to a non‐NF1 child. The pregnancies of non‐NF1 mothers giving birth to a NF1 child were 0.43 (95%CI 0.24–0.62) weeks shorter than in the control group. In summary, NF1 of the mother was associated with a shortened pregnancy and increased pregnancy complications. Also, the NF1 of the fetus slightly shortened pregnancy. Since mothers with NF1 are at increased risk for pregnancy complications, careful evaluation of their pregnancies is warranted.
Epilepsy in fragile‐X‐syndrome mimicking panayiotopoulos syndrome: Description of three patients
Authors: Bonanni Paolo , Casellato Susanna , Fabbro Franco , Negrin Susanna
Published: August 2017

Fragile‐X‐syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10–20% of individuals with Fragile‐X‐syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. We describe the clinical features, EEG findings and evolution in three patients affected by Fragile‐X‐syndrome and epilepsy mimicking Panayiotopoulos syndrome. Age at seizure onset was between 4 and about 7 years. Seizures pattern comprised a constellation of autonomic symptoms with unilateral deviation of the eyes and ictal syncope. Duration of the seizures could be brief or lengthy. Interictal EEGs revealed functional multifocal abnormalities. The evolution was benign in all patients with seizures remission before the age of 14. This observation expands the spectrum of benign epileptic phenotypes present in Fragile‐X‐syndrome and may be quite helpful in guiding anticonvulsant management and counseling families as to expectations regarding seizure remission.
New intragenic rearrangements in non‐Finnish mulibrey nanism
Authors: Jobic Florence , Morin Gilles , Vincent‐Delorme Catherine , Cadet Estelle , Cabry Rosalie , Mathieu‐Dramard Michèle , Copin Henri , Rochette Jacques , Jedraszak Guillaume
Published: August 2017

Prenatal growth is a complex dynamic process controlled by various genetic and environmental factors. Among genetic syndromes characterized by growth restriction, MULIBREY nanism represents a rare autosomal recessive condition presenting with severe pre‐ and post‐natal growth failure, characteristic dysmorphic features but normal neurological development. The phenotype of MULIBREY nanism is variable and overlaps with others such as the Silver‐Russell syndrome. We report here three patients in two distinct non‐Finnish families from North France who were first suspected to have Silver–Russell syndrome which failed to be confirmed on molecular analyses. Clinical features in the three patients led us to also consider the diagnosis of MULIBREY nanism. Sequencing of the TRIM37 gene showed the three patients shared a novel nonsense mutation (c.181 C>T p.Arg61*) in a heterozygous state. Quantitative fluorescent multiplex PCR identified a new deletion of exons 15 and 16 in TRIM37 in one isolated patient and another deletion of exon 9 in two siblings. Breakpoints of both the deletions were localized in Alu sequences. Given the high number of Alu repeats, which predispose to gene rearrangements, one should always consider such genetic rearrangements in the molecular diagnosis of non‐Finnish MULIBREY nanism patients. Early diagnosis of the disease would prompt careful cardiac follow up of such patients as cardiological complication is a characteristic feature of the MULIBREY nanism as described in this report.
Neonatal fractures as a presenting feature of LMOD3‐associated congenital myopathy
Authors: Abbott Megan , Jain Mahim , Pferdehirt Rachel , Chen Yuqing , Tran Alyssa , Duz Mehmet B. , Seven Mehmet , Gibbs Richard A. , Muzny Donna , Lee Brendan , Marom Ronit , Burrage Lindsay C.
Published: August 2017

Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family. All exhibited perinatal fractures, and thus, a skeletal dysplasia was considered as possibly contributing to the phenotype. However, whole exome sequencing revealed a homozygous, loss‐of‐function pathogenic variant in LMOD3, which has recently been associated with nemaline myopathy and, in a subset of patients, perinatal fractures. This case demonstrates the importance of considering congenital neuromuscular disorders in the differential diagnosis of perinatal fractures.
Paternal transmission of a FMR1 full mutation allele
Authors: Alvarez‐Mora Maria Isabel , Guitart Miriam , Rodriguez‐Revenga Laia , Madrigal Irene , Gabau Elisabeth , Milà Montserrat
Published: August 2017

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and autism. In most of cases, the molecular basis of this syndrome is a CGG repeat expansion in the 5′ untranslated region of the FMR1 gene. It is inherited as an X linked dominant trait, with a reduced penetrance (80% for males and 30% for females). Full mutation (FM) expansion from premutated alleles (PM) is only acquired via maternal meiosis, while paternal transmission always remains in the PM range. We present a 16‐year‐old girl with a mild fragile X syndrome phenotype. FMR1 gene study showed that the patient inherited a mosaic premutation‐full mutation with an unmethylated uninterrupted allele (175, >200 CGG) from her father. The father showed an 88 CGG uninterrupted unmethylated allele in blood and sperm cells. To our knowledge, this is the first case of a FMR1 mosaic premutation‐full mutation allele inherited from a PM father. In our opinion, the most likely explanation could be a postzygotic somatic expansion. We can conclude that in rare cases of a child with a full mutation whose mother does not carry a premutation, the possibility of paternal transmission should be considered.
Clinical and molecular characterization of de novo loss of function variants in HNRNPU
Authors: Leduc Magalie S. , Chao Hsiao‐Tuan , Qu Chunjing , Walkiewicz Magdalena , Xiao Rui , Magoulas Pilar , Pan Shujuan , Beuten Joke , He Weimin , Bernstein Jonathan A. , Schaaf Christian P. , Scaglia Fernando , Eng Christine M. , Yang Yaping
Published: August 2017

DNA alterations in the 1q43‐q44 region are associated with syndromic neurodevelopmental disorders characterized by global developmental delay, intellectual disability, dysmorphic features, microcephaly, seizures, and agenesis of the corpus callosum. HNRNPU is located within the 1q43‐q44 region and mutations in the gene have been reported in patients with early infantile epileptic encephalopathy. Here, we report on the clinical presentation of four patients with de novo heterozygous HNRNPU loss‐of‐function mutations detected by clinical whole exome sequencing: c.651_660del (p.Gly218Alafs*118), c.1089G>A (p.Trp363*), c.1714C>T (p.Arg572*), and c.2270_2271del (p.Pro757Argfs*7). All patients shared similar clinical features as previously reported including seizures, global developmental delay, intellectual disability, variable neurologic regression, behavior issues, and dysmorphic facial features. Features including heart defects and kidney abnormalities were not reported in our patients. These findings expands the clinical spectrum of HNRNPU‐related disorder and shows that HNRNPU contributes to a subset of the clinical phenotypes associated with the contiguous 1q43‐q44 deletion syndrome.
Preaxial polydactyly in an individual with Wiedemann‐Steiner syndrome caused by a novel nonsense mutation in KMT2A
Authors: Enokizono Takashi , Ohto Tatsuyuki , Tanaka Ryuta , Tanaka Mai , Suzuki Hisato , Sakai Aiko , Imagawa Kazuo , Fukushima Hiroko , Iwabuti Atsushi , Fukushima Takashi , Sumazaki Ryo , Uehara Tomoko , Takenouchi Toshiki , Kosaki Kenjiro
Published: August 2017

Wiedemann‐Steiner syndrome (WDSTS) is an autosomal dominant disorder characterized by hypertrichosis, intellectual disability, and dysmorphic facial appearances (down‐slanted vertically narrow palpebral fissures, wide nasal bridge, broad nasal tip, and thick eyebrows). In 2012, Jones and co‐workers identified heterozygous mutations in KMT2A (lysine methyltransferase 2A) as the molecular cause of WDSTS. Although the phenotype of this syndrome continues to expand, the associated features are not fully understood. Here, we report WDSTS in a 12‐year‐old Japanese boy with a novel nonsense mutation in KMT2A. He had right preaxial polydactyly, which has not been previously reported in WDSTS. We could not identify a causal relationship between the KMT2A mutation and preaxial polydactyly, and cannot exclude the preaxial polydactyly is a simple coincidence. We summarized the clinical features of WDSTS associated with KMT2A mutation and discussed the cardinal symptoms in detail.
Challenges of developing and conducting clinical trials in rare disorders
Authors: Kempf Lucas , Goldsmith Jonathan C. , Temple Robert
Published: August 2017

Rare disease drug development is a rapidly expanding field. Clinical researchers in rare diseases face many challenges when conducting trials in small populations. Disease natural history is often poorly understood and the ability to detect clinically meaningful outcomes requires understanding of their rate of occurrence and variability, both of which contribute to difficulties in powering a study. Standard trial designs are not optimized to obtain adequate safety and efficacy data from small numbers of patients, so alternative designs (enrichment, crossover, adaptive, N‐of 1) need to be considered. The affected patients can be hard to identify, especially early in the course of their disease, are generally geographically dispersed, and are often children. Trials are frequently conducted on an international scale and may be subject to complex or multiple regulatory agency oversights and may be affected by local customs, cultures, and practices. A basic understanding of the FDA programs supporting development of drugs for rare diseases is provided by this review and the role of early consultation with the FDA is emphasized. Of recent FDA New Molecular Entities (NME) approvals, 41% (17 approvals) in 2014, 47% (21 approvals) in 2015, and 41% (9 approvals) in 2016 were for rare disease indications. Through effective interactions and collaborations with physicians, institutions, and patient groups, sponsors have been successful in bringing new treatments to market for individuals affected by rare diseases. Challenges to drug development have been overcome through the focused efforts of patients/families, non‐profit patient advocacy groups, drug developers, and regulatory authorities.
A Semi‐Synthetic Glycoconjugate Vaccine Candidate for Carbapenem‐Resistant Klebsiella pneumoniae
Authors: Seeberger Peter H. , Pereira Claney L. , Khan Naeem , Xiao Guozhi , Diago‐Navarro Elizabeth , Reppe Katrin , Opitz Bastian , Fries Bettina C. , Witzenrath Martin
Published: August 2017

Hospital‐acquired infections are an increasingly serious health concern. Infections caused by carpabenem‐resistant Klebsiella pneumoniae (CR‐Kp) are especially problematic, with a 50 % average survival rate. CR‐Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross‐reactive antibodies against CR‐Kp CPS in mice and rabbits. Whole‐cell ELISA was used to establish the surface staining of CR‐Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi‐synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium.
Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design
Authors: Wu Yuteng , Villa Fabrizio , Maman Joseph , Lau Yu Heng , Dobnikar Lina , Simon Aline C. , Labib Karim , Spring David R. , Pellegrini Luca
Published: August 2017

The exploitation of synthetic lethality by small‐molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND‐1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the synthetic lethality approach. Herein, we report the design, optimization, and validation of double‐click stapled peptides encoding the Ctf4‐interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase α from the replisome in yeast extracts. Our study provides proof‐of‐principle evidence for the development of small‐molecule inhibitors of the human CTF4 orthologue AND‐1.
Direct and Stereospecific [3+2] Synthesis of Pyrrolidines from Simple Unactivated Alkenes
Authors: Otero‐Fraga Jorge , Suárez‐Pantiga Samuel , Montesinos‐Magraner Marc , Rhein Dennis , Mendoza Abraham
Published: August 2017

Pyrrolidines are important heterocyclic compounds with endless applications in organic synthesis, metal catalysis, and organocatalysis. Their potential as ligands for first‐row transition‐metal catalysts inspired a new method to access complex poly‐heterocyclic pyrrolidines in one step from available materials. This fundamental step forward is based on the discovery of an essential organoaluminum promoter that engages unactivated and electron‐rich olefins in intermolecular [3+2] cycloadditions.
Wacker‐Type Oxidation Using an Iron Catalyst and Ambient Air: Application to Late‐Stage Oxidation of Complex Molecules
Authors: Liu Binbin , Jin Fengli , Wang Tianjiao , Yuan Xiaorong , Han Wei
Published: August 2017

A practical and general iron‐catalyzed Wacker‐type oxidation of olefins to ketones is presented, and it uses ambient air as the sole oxidant. The mild oxidation conditions enable exceptional functional‐group tolerance, which has not been demonstrated for any other Wacker‐type reaction to date. The inexpensive and nontoxic reagents [iron(II) chloride, polymethylhydrosiloxane, and air] can, therefore, also be employed to oxidize complex natural‐product‐derived and polyfunctionalized molecules.
Solvatation als Ursache für die unerwartete Nucleophilie‐Reihung von Peroxid‐Anionen
Authors: Mayer Robert J. , Tokuyasu Takahiro , Mayer Peter , Gomar Jérôme , Sabelle Stéphane , Mennucci Benedetta , Mayr Herbert , Ofial Armin R.
Published: August 2017

Die nucleophilen Reaktivitäten (N, sN) von Peroxid‐Anionen (aus aromatischen und aliphatischen Persäuren oder Alkylhydroperoxiden generiert) wurden durch Messung der Kinetik ihrer Reaktionen mit Benzhydrylium‐Ionen (Ar2CH+) in alkalischer wässriger Lösung bei 20 °C bestimmt. Überraschenderweise reagieren die Peroxycarboxylate RCO3− trotz ihrer deutlich geringeren Brønsted‐Basizität viel schneller als die Alkylperoxid‐Anionen ROO−. Einsetzen der Geschwindigkeitskonstanten ihrer Reaktionen mit Benzhydrylium‐Ionen in die lineare Freie‐Energie‐Beziehung lg k=sN(N+E) lieferte die Nucleophilie‐Parameter (N, sN) der Peroxid‐Anionen, die es ermöglichten, Geschwindigkeiten von Weitz‐Scheffer‐Epoxidierungen vorherzusagen. Um die beobachtete Reaktivitätsreihung zu erklären, wurden DFT‐Rechnungen durchgeführt, wobei Lösungsmitteleffekte durch die “Integral‐Equation‐Formalism”‐Version des “Polarizable Continuum Model” berücksichtigt wurden.
Reagent‐Free C−H/N−H Cross‐Coupling: Regioselective Synthesis of N‐Heteroaromatics from Biaryl Aldehydes and NH3
Authors: Zhao Huai‐Bo , Liu Zhan‐Jiang , Song Jinshuai , Xu Hai‐Chao
Published: August 2017

An unprecedented synthesis of N‐heteroaromatics from biaryl aldehydes and NH3 through reagent‐free C−H/N−H cross‐coupling has been developed. The electrosynthesis uses NH3 as an inexpensive and atom‐economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N‐heteroaromatic products.
Electroless Formation of Hybrid Lithium Anodes for Fast Interfacial Ion Transport
Authors: Choudhury Snehashis , Tu Zhengyuan , Stalin Sanjuna , Vu Duylinh , Fawole Kristen , Gunceler Deniz , Sundararaman Ravishankar , Archer Lynden A.
Published: August 2017

Rechargeable batteries based on metallic anodes are of interest for fundamental and application‐focused studies of chemical and physical kinetics of liquids at solid interfaces. Approaches that allow facile creation of uniform coatings on these metals to prevent physical contact with liquid electrolytes, while enabling fast ion transport, are essential to address chemical instability of the anodes. Here, we report a simple electroless ion‐exchange chemistry for creating coatings of indium on lithium. By means of joint density functional theory and interfacial characterization experiments, we show that In coatings stabilize Li by multiple processes, including exceptionally fast surface diffusion of lithium ions and high chemical resistance to liquid electrolytes. Indium coatings also undergo reversible alloying reactions with lithium ions, facilitating design of high‐capacity hybrid In‐Li anodes that use both alloying and plating approaches for charge storage. By means of direct visualization, we further show that the coatings enable remarkably compact and uniform electrodeposition. The resultant In‐Li anodes are shown to exhibit minimal capacity fade in extended galvanostatic cycling when paired with commercial‐grade cathodes.