bluuebunny/crossref_metadata_2025 huggingface dataset:
Egg Activation
Authors: Zhang Zijing , Wolfner Mariana F , Williams Carmen J
Published: January 2018

Egg activation is the process of converting the female gamete, known as an oocyte or egg, into a cell that can support embryogenesis. In many organisms, this process is triggered by the fertilising sperm, but some organisms trigger egg activation by other mechanisms. Here we review the physiological state of the egg before activation, the mechanisms used to initiate egg activation, and the downstream cellular changes that must occur for a successful transition into a developing embryo. We will consider egg activation as it occurs in both invertebrate and vertebrate model systems, highlighting key similarities and differences between them.

Key Concepts

Animal eggs must undergo a process of ‘activation’ to allow them to initiate embryo development.

Egg activation transitions a mature – but arrested – oocyte to a totipotent cell that can initiate mitosis and embryogenesis.

Activation is triggered by a rise in calcium that sweeps across the egg in wave(s).

The calcium wave is triggered by fertilisation in vertebrates, echinoderms, and molluscs and by sperm‐independent mechanical triggers in insects.

The calcium wave is propagated through release of calcium from internal stores.

The calcium rise triggers events including completion of meiosis, reorganisation of the sperm nucleus into a male pronucleus, translation of some stored maternal mRNAs and destruction of others in the egg, modulation of the phosphoproteome of the egg, and modification of the egg's membranes and external coverings to block fertilisation by additional sperm.
Chromosomes 21 and 22: Gene Density
Authors: Saccone Salvatore , Bernardi Giorgio
Published: January 2018

Isochores are long DNA (deoxyribonucleic acid) segments that are fairly homogeneous in base composition. The GC (guanine+cytosine)‐richest and GC‐poorest isochores of the genomes from warm‐blooded vertebrates are characterised by the highest and the lowest gene concentrations, respectively. They correspond to specific types of chromosomal bands, namely the GC‐richest isochores are in the subset of R‐positive bands generally located at the telomeric chromosomal end and the GC‐poorest are in the darker G‐positive bands. The distribution of the isochores along the chromosomes determines the formation of the light/dark G/R bands, with the compositional difference at the local level having a great relevance. Chromosomes 21 and 22 can be used to show some properties of both the GC‐richest and GC‐poorest isochores of the human genome, being composed by chromosomal bands covering the entire range of GC composition, from the GC‐poorest L1
+
bands to the GC‐richest H3
+
bands.

Key Concepts

The human genome is composed of two compartments endowed with very different genomic properties.

The GC‐richest genomic compartment is prevalently composed of isochores from the H2 and H3 families.

The GC‐poorest genomic compartment is prevalently composed of isochores from the L1 family.

The GC‐richest and the GC‐poorest genomic compartments are located, in the mitotic chromosomes, distantly from one another.

The GC‐richest and the GC‐poorest genomic compartments correspond to the gene‐richest and the gene‐poorest region, respectively.

The GC‐richest and the GC‐poorest genomic compartments are located in the inner part and at the periphery of the cell nuclei.

Human chromosomes 21 and 22 summarise all the properties endowed with the GC‐richest and the GC‐poorest regions.
Ion Channels and Human Disorders
Authors: Raja Rayan Dipa L , Hanna Michael G
Published: January 2018

The human channelopathies are a rapidly expanding group of primarily genetic conditions. They are characterised by dysfunction of membrane‐bound glycoproteins (ion channels). Several neurological and general medical disorders have been shown to be owing to underlying ion‐channel dysfunction and genetic analysis is now often a routine clinical practice. These disorders exhibit extensive phenotypic and genetic heterogeneity with many distinct diseases caused by dysfunction of the same channel by differing mechanisms. With the advent of the next‐generation sequencing, we are discovering even greater genetic heterogeneity and our understanding of the mechanisms behind these diseases continues to extend as more functional analysis is performed and new techniques are developed. In the future, this will lead to the identification of better targeted treatments for these diseases.

Key Concepts

Channelopathies are commonly owing to mutations in functionally important regions of either pore‐forming or auxiliary channel subunits resulting in episodic disorders.

Mutations often cause disease by altering channel gating, voltage dependence or channel assembly and now there is also evidence for effects in posttranslational modification.

Channelopathies are now understood to present either with intermittent symptoms which may completely recover, have a secondary progression or may be a severe primary progressive disease. The location and type of the mutation often influence this.

Genetic heterogeneity is very common amongst the channelopathies and is likely to increase with the use of modern genetic analysis.

Channelopathies, such as myotonia congenita, have extensive phenotypic variability even within a single pedigree, making it difficult to predict and give accurate genetic counselling.
Genetic Linkage Mapping
Authors: Imai‐Okazaki Atsuko , Ott Jurg
Published: January 2018

Random occurrences of crossovers along a chromosome permit definition of a genetic distance. Such distances are used to create genetic maps and localise disease genes on these maps. Human genetic maps consist of dense sets of DNA polymorphisms, notably single‐nucleotide polymorphisms (SNPs) and, resulting from DNA sequencing, single‐nucleotide variants (SNVs). The main application of linkage mapping is to localise hypothesised disease genes on the human marker maps, which in turn represents the first step towards understanding of disease aetiology. While linkage analysis represents the mainstay for genetic mapping, newer approaches have been developed, for example, methods allowing the use of a single affected individual in conjunction with a number of control individuals, a situation not tractable by standard linkage and genetic association analyses.

Key Concepts

Genetic distances are based on the random occurrence of crossovers along a chromosome, and a crossover will lead to a recombination in half of the gametes.

Genetic loci in close proximity will rarely experience a recombination between them, so the recombination fraction will be small.

For short distances, the recombination fraction represents genetic distance in units of Morgans.

DNA sequencing has established the order of variants on a chromosome, so genetic linkage mapping essentially aims to measure distances in each interval (between two adjacent variants) on a chromosome.

Disease gene mapping hypothesises the presence of a disease locus, for which genetic distances to one after another genetic variant are estimated. A significantly small such distance (recombination fraction significantly smaller than 50%) establishes genetic linkage between the disease locus and a given variant.
Renal Carcinoma and
von H
ippel–
L
indau Disease
Authors: Connor Thomas M , Maxwell Patrick H
Published: January 2018

von Hippel–Lindau (VHL) disease is a rare autosomal dominant condition with a high risk of renal carcinoma. The underlying tumour suppressor gene is also mutated in most sporadic clear cell renal carcinomas. The
VHL
gene product functions as an E3 ubiquitin ligase that mediates the degradation of the hypoxia‐inducible factor (HIF). Loss of
VHL
leads to constitutive activation of HIF target genes that normally mediate responses to hypoxia, including those that regulate diverse processes such as angiogenesis and cellular metabolism. Novel therapies for renal cancer target angiogenesis mediated by the vascular endothelial growth factor (VEGF). Renal cancers also exhibit common driver mutations subsequent to
VHL
loss, which influence pathways involved in chromatin remodelling and mammalian target of rapamycin (mTOR) signalling. A number of other kidney cancer genes have been found from studying other familial cancer syndromes. These genes are involved in metabolism and responses to cellular stress and nutrient deprivation.

Key Concepts

von Hippel–Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by mutations in the
VHL
tumour suppressor gene.

VHL disease exhibits a striking genotype–phenotype correlation.

The great majority of sporadic clear cell renal cancers also show loss of VHL function.

The VHL gene product functions as an E3 ubiquitin ligase that mediates the degradation of hypoxia‐inducible factor (HIF) alpha.

Loss of VHL leads to constitutive activation of HIF target genes that play key roles in angiogenesis and metabolism.

Novel therapies for renal cancer target specific effects of VHL loss, including inhibitors of angiogenesis.

Renal cancers exhibit common driver mutations affecting chromatin remodelling and nutrient signalling.

A number of other kidney cancer genes have been found to be involved in cellular pathways involved in cellular stress and nutrient deprivation.
Molecular Genetics ofEmery–Dreifuss Muscular Dystrophy
Authors: Meinke Peter
Published: January 2018

Emery–Dreifuss muscular dystrophy (EDMD) is a rare neuromuscular disorder typically characterised by early contractures, slowly progressive muscular wasting and life‐threatening heart conduction disturbances, which can develop into a cardiomyopathy. There is a wide intrafamilial and interfamilial clinical variability. Genetically, X‐linked recessive, autosomal dominant and autosomal recessive forms can be distinguished. Female carriers of the X‐linked forms may manifest with cardiac symptoms. By molecular genetic methods, EDMD can be associated with mutations in several genes encoding nuclear envelope proteins. These proteins are lamin A, emerin, FHL1, nesprins and SUN proteins. Still only approximately half of unrelated patients diagnosed with EDMD have a mutation in known genes pointing to further genetic heterogeneity in EDMD. The molecular pathogenesis is not fully resolved, but there are effects on signalling, mechanical stability and gene expression.

Key Concepts

Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder recognised clinically by three features: early contractures, a characteristic pattern of muscle wasting and cardiac conduction defects.

EDMD was originally described as an X‐linked disorder, later found to be caused by mutations in theEMDgene encoding a nuclear membrane protein, emerin.

Molecular genetic analysis allows precise subtyping of EDMD into X‐linked forms (EMDandFHL1associated), autosomal dominant forms (LMNA,SYNE1/SYNE2associated) and autosomal recessive forms (LMNAandSUN1associated).

Wide clinical variability of EDMD and clinical overlap with other clinical entities frequently require consideration of patients not completely fulfilling the EDMD diagnostic criteria for molecular genetic differentiation inEMD,LMNA,SYNE1/SYNE2,SUN1andFHL1.

Digenic pathogenesis has been observed includingLMNA/EMD,LMNA/DES,SYNE1/SYNE2,LMNA/SUN1,LMNA/SUN2andEMD/SUN1.

In all cases, EDMD mutations affect proteins located at the nuclear envelope where they interact with each other.

Many patients do not have mutations in genes identified so far, so further genes are expected to be involved in the pathogenesis of EDMD.
Non‐B DNAStructure and Mutations Causing Human Genetic Disease
Authors: Bacolla Albino , Cooper David N , Vasquez Karen M , Tainer John A
Published: January 2018

Besides the canonical right‐handed double helix, biologically important noncanonical deoxyribonucleic acid (DNA) secondary structures have been characterised, including quadruplexes, triplexes, slipped/hairpins, Z‐DNA and cruciforms, collectively termed non‐B DNA. Formation of non‐B DNA is mediated by repetitive sequence motifs, such as G‐rich sequences, purine/pyrimidine tracts, direct (tandem) repeats, alternating purine–pyrimidines and inverted repeats, respectively. Such repeats are abundant in the human genome and non‐B DNA occurs at specific genomic locations, supporting a role in gene regulation, RNA translation and protein function. Repetitive motifs are also found at sites of chromosomal alterations associated with both human genetic disease and cancer. Characterised by an inherent capacity to expand spontaneously, such sequences not only cause >30 neurological diseases but may also contribute to disease susceptibility. The formation of non‐B DNA structures is believed to promote genomic alterations by impeding efficient and error‐free DNA replication, transcription and repair.

Key Concepts

The structure of DNA is polymorphic as well as its sequence; besides canonical right‐handed double helix (B‐DNA), repetitive sequences can also adopt alternative (non‐B DNA) conformations such as quadruplexes, triplexes, slipped/hairpins, Z‐DNA and cruciforms.

Repetitive DNA sequences are found at particular locations within many human genes, suggesting that they can affect transcription and encode homopolymeric amino acid runs that are important for protein–protein and protein–DNA/RNA interactions.

G4 and Z‐DNA structures have been detected in cells through specific antibodies, mostly in correspondence of actively transcribed genes and, in the case of G4, at telomeres.

Copy number variation (CNV) is a form of genetic alteration that, by involving thousands of loci in the genome, contributes to human individuality.

Repetitive sequences capable of forming non‐B DNA are found at sites of chromosomal breaks, CNVs and other rearrangements such as translocations, deletions and gene conversion events, which can contribute to human genetic disease and cancer.

The recurrent translocation t(22;11) events associated with Emanuel syndrome are mediated by cruciform structures that occur at inverted repeats.

Tandem repeats (microsatellites) may expand within gene sequences, contributing to more than 30 neurological diseases; present in a variable number in genes in the population, they may contribute to human disease susceptibility.

An increasing number of enzymes are being reported that resolve non‐B DNA and RNA structures, and whose mutations lead to genomic instability and human disease; however, in some cases, the recognition of non‐B DNA structures is the cause of genetic instability.

lncRNAs repress gene expression by forming triplex structures with their target duplex DNA.

Non‐B DNA structures stimulate mutations via mechanisms that alter DNA synthesis, transcription and repair.
Activity‐Based Protein Profiling
Authors: van Rooden Eva J , Bakker Alexander T , Overkleeft Herman S , van der Stelt Mario
Published: January 2018

Activity‐based protein profiling is a method to study a subset of the enzymatically active proteome. This method uses chemical probes that covalently react with active enzymes. These labelled proteins can subsequently be analysed by means of a detection tag on the probe. A diverse set of probes has been developed for many enzyme classes, such as serine hydrolases, proteases, glycosidases and kinases. Different analytical techniques are currently available to visualise, identify and quantify probe‐labelled proteins with high efficiency. Activity‐based protein profiling has well‐developed applications in discovering new drug targets and in profiling inhibitors for potency and selectivity. Activity‐based protein profiling will, therefore, continue to aid research both in fundamental biology and drug discovery.

Key Concepts

Activity‐based protein profiling (ABPP) is a method to study an enzymatically active subset of the proteome and complements abundance‐based proteomics.

An activity‐based probe is a compound that covalently labels only the active form of an enzyme.

Activity‐based probes have been developed for several classes of enzymes, such as serine hydrolases, proteases, lipases and kinases.

Every ABPP experiment consists of two parts: an activity‐dependent labelling part, followed by an analytical part to visualise and characterise this labelling event.

Different analytical platforms have been developed for ABPP, including SDS‐PAGE, LC‐MS, CE‐LIF, FluoPol, EnPlex and microarray platforms.

ABPP is mainly used for target discovery by comparing different proteomes (comparative ABPP) and for characterising inhibitor selectivity and potency (competitive ABPP).

ABPP is a powerful method for drug discovery.

It is surprising that ABPP is not more widely used outside of specialised labs developing new probes.
Immunity against Hepatitis
B
Virus and
HBV
Vaccines
Authors: Doi Hiroyoshi , Morikawa Kenichi , Kanto Tatsuya
Published: January 2018

Hepatitis B virus (HBV) remains a global health problem, with 257 million carriers in 2015. Birth‐dose administration of hepatitis B vaccine (HB vaccine) has significantly reduced the numbers of HBV carriers in high‐endemic countries. The clinical course of infection is dependent on viral and host factors. It is known from patients with acute hepatitis that vigorous innate and adaptive immunity is needed to clear HBV. However, HBV employs covalently closed circular DNA – a mini chromosome in the nucleus – as a replicative template that helps the virus to hide under the radar of the host immunosurveillance system, and once HBV escapes from immune clearance, pervasive impairment of various immune cells is observed in chronically infected patients. In such circumstances, complete HBV eradication is rarely attainable despite lifelong treatment with nucleos(t)ide analogues. Functional cure, the state of HB surface antigen loss, is a surrogate clinical target for patients at risk of progression to cirrhosis and hepatocellular carcinoma. Appropriate induction of both innate and adaptive immunity is vital to achieve a functional cure. Understanding the immune reaction against HBV and its impact on the clinical course of acute and chronic hepatitis, along with recent advances in HB vaccination, is key to combating this infection.

Key Concepts

HBV infection is a worldwide health problem that causes potentially life‐threatening liver diseases, such as liver cirrhosis and hepatocellular carcinoma.

HBV cccDNA exists as a mini chromosome in the nucleus of infected hepatocytes and works as a replicative template for the production of progeny virus or HBV‐related proteins.

The outcomes of primary HBV infection are influenced by the age of the host at the time of exposure.

Adult patients with acute HBV infection eradicate HBV by robust activation of innate and adaptive immune reactions.

Chronic HBV infection impairs the function of various immune cells, leading to the difficulty of HBV elimination.

Implementation of HB vaccine in endemic countries has contributed significantly to the reduction of HBsAg‐positive carriers in the world.
Zika Virus
Authors: Harper David R , Litaker John , Logan James
Published: January 2018

Zika virus is closely related to the viruses causing yellow fever, West Nile or Dengue fever and, similar to them, is an arbovirus, actively transmitted by mosquito vectors. Sexual transmission between humans also occurs.

Zika virus was not associated with serious human disease until after its arrival in the Americas. Since 2015 it has been associated with a range of pathologies. The most significant is congenital Zika syndrome, marked by foetal microcephaly.

The number of Zika infections has fallen since 2016. Confirmed infections in the Americas total over 200 000 cases, with more than 50% of these in Brazil. Deaths are rare, and congenital effects have been the major concern, particularly in Brazil, where more than 80% of such cases have occurred. The reasons for this high rate are unclear, although poverty is often cited as a likely contributor.

Eighty‐four countries or territories worldwide have had evidence of mosquito‐borne Zika virus transmission. Relatively small numbers of infections have been reported in the United States, with transmission restricted to the far south of Texas and Florida.

There is no vaccine or antiviral drug effective against Zika. The best preventive measures as of 2017 involve controlling or avoiding the vector mosquitoes.

Key Concepts

Zika virus is a Flavivirus with an RNA genome, related to other viruses such as yellow fever, West Nile and Dengue fever.

The virus was identified in Africa in 1947 and exists as two broad lineages, African and Asian.

The virus is an arbovirus (arthropod‐borne virus), spread by bites from vector mosquitoes of the genusAedes, although direct person to person transmission also occurs.

Historically, most people infected with Zika did not develop symptoms, and even when they did these were relatively mild.

Until 2007, Zika virus infection was restricted to an equatorial belt in Africa and Asia, but in 2015, the Asian form of Zika was identified in Brazil, the first time it was seen in the Americas. By the end of 2016, more than 100 000 confirmed cases had occurred in Brazil.

Later in 2015, Zika infection was associated with severe forms of microcephaly in newborns, predominantly in the northeast of Brazil.

Zika infection has also been associated with the autoimmune‐mediated Guillain–Barré syndrome.

In 2017, numbers of infections in the Americas have dropped sharply, but the virus continues to spread, with mosquito‐borne infections seen in 84 countries and territories around the world.

There is no vaccine or therapeutic drug for Zika virus, although clinical trials are proceeding. The best strategy at present is to control mosquitoes and avoid mosquito bites.

Future control approaches need to be informed by effective public health surveillance to support both analysis and response.
Evolutionary History of Vipers
Authors: Alencar Laura RV , Martins Marcio , Greene Harry W
Published: January 2018

Vipers are venomous snakes characterised by having two enlarged highly mobile fangs. They comprise more than 300 species belonging to the Viperidae, which in turn includes viperines (or ‘true vipers’), azemiopines and crotalines (or ‘pitvipers’). They first radiated in the Old World more than 50 million years ago and later rapidly diversified in the New World. Several interesting traits emerged during their evolutionary history, including thermosensitive loreal pits and parental care in crotalines and specialised sound production in rattlesnakes. Vipers are currently found in almost every available habitat on earth and occupy diverse ecological niches. Ancestrally, they evolved the ability to eat unusually heavy, bulky prey and exhibit an impressive range of diet specialisations. Although vipers represent an interesting and successful radiation, many species are threatened with extinction and several aspects of their evolutionary history still need investigation.

Key Concepts

Vipers represent one of three extant groups of snakes in which a front‐fanged venomous system evolved.

Vipers belong to the family Viperidae comprising the subfamilies Viperinae, Azemiopinae and Crotalinae.

Oldest viper fossils are from the lower Miocene, but molecular phylogenies suggest an older origin for Viperidae, dating back to the early Eocene.

Vipers originated in the Old World with pitvipers later invading the New World and rapidly spreading throughout North, Central and South America.

Besides an advanced venom delivery system, other key features emerged during the evolution of vipers such as loreal pits characterising all pitvipers and the rattle of rattlesnakes.

The several unique features characterising vipers allowed them to diversify into a wide range of ecological niches.

Vipers evolved into different diets, comprising both generalists and those specialised in specific prey types, such as lizards, mammals, birds or frogs.

Arboreal habits, nocturnal and diurnal activities and different reproductive modes also evolved in several lineages of vipers.
Cell transplantation strategies for acquired and inherited disorders of peripheral myelin
Authors: Muhammad A. K. M. G. , Kim Kevin , Epifantseva Irina , Aghamaleky‐Sarvestany Arwin , Simpkinson Megan E. , Carmona Sharon , Landeros Jesse , Bell Shaughn , Svaren John , Baloh Robert H.
Published: January 2018

Objective

To investigate transplantation of rat Schwann cells or human iPSC‐derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage.

Methods

Primary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation. Human‐induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells, and subsequently toward a Schwann cell lineage via two different protocols. Cell types were characterized using flow cytometry, immunocytochemistry, and transcriptomics. Rat Schwann cells and human iPSC derivatives were transplanted into (1) nude rats pretreated with lysolecithin to induce demyelination or (2) a transgenic rat model of dysmyelination due to PMP22 overexpression.

Results

Rat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration. Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal‐appearing myelin. Human iPSC‐derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin.

Interpretation

These results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve. However, lack of reliable technology for generating human iPSC‐derived Schwann cells for transplantation therapy remains a barrier in the field.
Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy
Authors: Lv Rui‐Juan , Ren Hai‐Tao , Guan Hong‐Zhi , Cui Tao , Shao Xiao‐Qiu
Published: January 2018

Objective

The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size.

Methods

This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new‐onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period.

Results

A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti‐VGKC in 23 patients (37.70%), anti‐NMDA‐R in 9 patients (14.75%), anti‐GABAB‐R in 6 patients (9.84%), and anti‐amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures.

Significance

This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new‐onset seizures in isolation or with a seizure‐predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural‐specific autoantibodies does not rule out AE.
Charcot Marie Tooth disease type 4J with complex central nervous system features
Authors: Orengo James P. , Khemani Pravin , Day John W. , Li Jun , Siskind Carly E.
Published: January 2018

We describe a family with Charcot Marie Tooth disease type 4J presenting with features of Charcot Marie Tooth disease plus parkinsonism and aphemia. Genetic testing found two variants in the FIG4 gene: c.122T>C (p.I41T) – the most common Charcot Marie Tooth disease type 4J variant – and c.1949‐10T>G (intronic). Proband fibroblasts showed absent FIG4 protein on western blot, and skipping of exon 18 by RT‐PCR. As most patients with Charcot Marie Tooth disease type 4J do not have central nervous system deficits, we postulate the intronic variant and I41T mutation together are causing loss of FIG4 protein and subsequently the central nervous system findings in our family.
Post‐transplant adaptive function in childhood cerebral adrenoleukodystrophy
Authors: Pierpont Elizabeth I. , McCoy Erin , King Kelly E. , Ziegler Rich S. , Shanley Ryan , Nascene David , Raymond Gerald V. , Phelan Rachel , Lund Troy C. , Orchard Paul J. , Miller Weston P.
Published: January 2018

Objective

Hematopoietic stem cell transplantation (HSCT) is the only treatment known to slow or halt inflammatory demyelination among boys with the cerebral form of X‐linked adrenoleukodystrophy (cALD), a devastating childhood condition affecting the central nervous system. HSCT can lead to a range of adverse outcomes including fatality. Previous studies have examined the potential predictors of post‐HSCT survival and neurologic functioning. However, little is known about patients' daily‐life adaptive functional outcomes (i.e., ability to communicate, maintain social relationships, and independently execute tasks of daily living). The purpose of this retrospective cohort study was to identify which patient characteristics and treatment‐related variables predict long‐term adaptive function among the survivors of HSCT for cALD.

Methods

We obtained caregiver ratings of adaptive functioning of 65 transplant survivors at an average of 4.6 years (range: 1.0–24.1 years) post‐HSCT. Using linear regression with penalized maximum likelihood estimation, we modeled the relative contribution of pre‐transplant neurocognitive test performance, MRI severity, transplant regimen, and length of time since transplant on patient adaptive functioning outcomes.

Results

Higher radiographic disease severity and poorer performance on baseline neurocognitive tests requiring fine motor skills and visual perception were associated with inferior adaptive functioning after HSCT. Use of radiation during the transplant preparative regimen also predicted poorer adaptive outcomes.

Interpretation

In addition to radiological disease severity, baseline neurocognitive test performance is associated with post‐transplant adaptive functional outcomes. Neurocognitive measures may play an important role in prognostic counseling and post‐transplant treatment planning for patients considering HSCT for cALD.
Inflammatory mediator expression within retrieved clots in acute ischemic stroke
Authors: Baek Byung Hyun , Kim Hyung Seok , Yoon Woong , Lee Yun Young , Baek Jang Mi , Kim Eun Hee , Kim Seul Kee
Published: January 2018

Objective

In this study we investigate the association between the expression of inflammatory mediators measured in clots retrieved by mechanical thrombectomy, stroke etiology, and the susceptibility vessel sign (SVS) on gradient‐echo (GRE) MR imaging in acute ischemic stroke patients.

Methods

We performed molecular analysis of intracranial clots retrieved by mechanical thrombectomy from 82 patients with acute stroke. Seventy‐two of these patients underwent GRE imaging before endovascular therapy. We measured the relative expression of inflammatory mediators by performing the quantitative real‐time polymerase chain reaction on the retrieved clots and assessed associations between the expression of inflammatory mediators and stroke subtypes as well as with GRE SVS.

Results

Classifications of stroke etiology for the cohort were as follows: cardioembolism (51, 62.2%), large artery atherosclerosis (9, 11%), and undetermined etiology (22, 26.8%). Clots associated with large artery atherosclerosis showed significantly higher interleukin (IL)‐1β expression than clots from both cardioembolism and undetermined etiology (P = 0.008). A positive SVS was identified in 48 of 72 patients (66.7%) who had GRE imaging. IL‐1β, tumor necrosis factor‐α, and matrix metalloproteinase‐9 expressions were significantly higher in clots with a negative SVS than in those with a positive SVS (P = 0.010, 0.049, and 0.004, respectively).

Interpretation

Expression of inflammatory mediators in intracranial clots differs significantly based on stroke etiology or presence or the absence of SVS on GRE imaging. This study suggests that molecular analysis of inflammatory mediators in retrieved clots is a promising tool for determining stroke mechanism in acute ischemic stroke patients.
From Compartmentalization of Bacteria within Inorganic Macrocellular Beads to the Assembly of Microbial Consortia
Authors: Roucher Armand , Morvan Mickaël , Pekin Deniz , Depardieu Martin , Blin Jean‐Luc , Schmitt Véronique , Konrad Manfred , Baret Jean‐Christophe , Backov Rénal
Published: January 2018

Microorganisms are highly efficient biocatalysts. Yet making use of their capabilities for chemical transformations requiring synergistic interactions between different microbes is challenging as the competition for resources might reduce the diversity and ultimately disrupt the synergies. Here, a new method is proposed for constructing microbial consortia for the integration of multistep transformations. Bacteria are successively grown and trapped within semipermeable inorganic foams produced as millimeter‐sized beads. The beads function as efficient living biocatalysts is demonstrated. These living heterogeneous biocatalysts are manipulated to perform cycles of biochemical reactions and furthermore assembled to perform preprogrammed sequences of reactions. This new family of living advanced biocatalysts should find applications in a wide range of basic research and industrial systems where complex tasks have to be performed by controlled consortia of microorganisms.
Decomposable s‐Tetrazine Copolymer Enables Single‐Walled Carbon Nanotube Thin Film Transistors and Sensors with Improved Sensitivity
Authors: Li Zhao , Ding Jianfu , Guo Chang , Lefebvre Jacques , Malenfant Patrick R. L.
Published: January 2018

Semiconducting single‐walled carbon nanotubes (sc‐SWCNTs) enriched by a conjugated polymer extraction process have been actively studied for various applications in both electronics and optoelectronics. Although the resulting tube samples usually have high sc‐purity and concentration, SWCNT networks from such dispersions typically contain residual conjugated polymer that may degrade device performance and its removal remains a challenge while maintaining uniform, dense SWCNT thin film networks. In this study, a novel polymer–SWCNT combination based on an alternating bisfuran‐s‐tetrazine and benzo[1,2‐b:4,5‐b′]dithiophene copolymer abbreviated as PBDTFTz is proposed. This polymer decomposes at >250 °C or under UV irradiation. In situ transistor characterization under laser irradiation confirms the polymer decomposition. The study of the tube network in the transistor channel at various channel lengths reveals significantly reduced contact resistance attributed to removal of the wrapping PBDTFTz polymer. In ammonia sensing experiments, sc‐SWCNT networks demonstrate rapid and reversible responses, while the unwrapped nanotube networks prove superior in terms of signal to noise ratio and a detection limit of 2.5 ppb is calculated, almost four times better than polymer wrapped nanotubes.
A Novel Room‐Temperature Multiferroic System of Hexagonal Lu1−xInxFeO3
Authors: Liu Juan , Sun Tu Lai , Liu Xiao Qiang , Tian He , Gao Ting Ting , Chen Xiang Ming
Published: January 2018

In the present work, h‐RFeO3 multiferroic ceramics are designed and created by introducing chemical pressure (In‐substitution for Lu) in LuFeO3. Lu1−xInxFeO3 (x = 0‐0.75) ceramics are prepared by the standard solid‐state reaction process. The crystal structure of the present ceramics is tuned from centrosymmetric Pbnm (x = 0) to non‐centrosymmetric P63cm (x = 0.4–0.6), and subsequently to centrosymmetric P63/mmc (x = 0.75), while the Pbnm and P63cm biphase structure is detected for x = 0.25. The Curie temperature for the polar P63cm (x = 0.4–0.6) phase decreases from >1000 to ≈550 K with increasing x. Cloverleaf ferroelectric domain structures are determined in polar Lu0.5In0.5FeO3 samples, and the ferroelectric domain walls at atomic scale are evaluated by the aberration‐corrected high‐angle annular dark‐field scanning transmission electron microscopy (HAADF STEM), where the spontaneous polarization of 1.73 µC cm−2 is determined for x = 0.5. The spontaneous polarization is also confirmed by calculating the site displacement from the centrosymmetric phase based on the X‐ray diffraction (XRD) data. Meanwhile, two magnetic transitions are determined for all compositions, that is, paramagnetic to antiferromagnetic transition at Néel temperature TN (≈350 K for x = 0.4–0.6), and antiferromagnetic to weak‐ferromagnetic transition at spin‐reorientation temperature TSR. The co‐presence of ferroelectric and antiferromagnetic orders confirms the present ceramics as promising room‐temperature multiferroic materials.
Surface‐Functionalization‐Mediated Direct Transfer of Molybdenum Disulfide for Large‐Area Flexible Devices
Authors: Shinde Sachin M. , Das Tanmoy , Hoang Anh Tuan , Sharma Bhupendra K. , Chen Xiang , Ahn Jong‐Hyun
Published: January 2018

The transfer of synthesized large‐area 2D materials to arbitrary substrates is expected to be a vital step for the development of flexible device fabrication processes. The currently used hazardous acid‐based wet chemical etching process for transferring large‐area MoS2 films is deemed to be unsuitable because it significantly degrades the material and damages growth substrates. Surface energy‐assisted water‐based transfer processes do not require corrosive chemicals during the transfer process; however, the concept is not investigated at the wafer scale due to a lack of both optimization and in‐depth understanding. In this study, a wafer‐scale water‐assisted transfer process for metal–organic chemical vapor‐deposited MoS2 films based on the hydrofluoric acid treatment of a SiO2 surface before the growth is demonstrated. Such surface treatment enhances the strongly adhering silanol groups, which allows the direct transfer of large‐area, continuous, and defect‐free MoS2 films; it also facilitates the reuse of growth substrate. The developed transfer method allows direct fabrication of flexible devices without the need for a polymeric supporting layer. It is believed that the proposed method can be an alternative defect‐ and residue‐free transfer method for the development of MoS2‐based next‐generation flexible devices.
DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for Guest Encapsulation and Cellular Delivery
Authors: Rahbani Janane F. , Vengut‐Climent Empar , Chidchob Pongphak , Gidi Yasser , Trinh Tuan , Cosa Gonzalo , Sleiman Hanadi F.
Published: January 2018

Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid‐like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single‐molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye‐mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer‐coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.
DNA Nanostructure‐Based Systems for Intelligent Delivery of Therapeutic Oligonucleotides
Authors: Hu Qinqin , Wang Sheng , Wang Lihua , Gu Hongzhou , Fan Chunhai
Published: January 2018

In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life‐threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine–phosphate–guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat–Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure‐based systems for the delivery of therapeutic oligonucleotides are discussed.
High‐Strength Nanotwinned Al Alloys with 9R Phase
Authors: Li Qiang , Xue Sichuang , Wang Jian , Shao Shuai , Kwong Anthony H. , Giwa Adenike , Fan Zhe , Liu Yue , Qi Zhimin , Ding Jie , Wang Han , Greer Julia R. , Wang Haiyan , Zhang Xinghang
Published: January 2018

Light‐weight aluminum (Al) alloys have widespread applications. However, most Al alloys have inherently low mechanical strength. Nanotwins can induce high strength and ductility in metallic materials. Yet, introducing high‐density growth twins into Al remains difficult due to its ultrahigh stacking‐fault energy. In this study, it is shown that incorporating merely several atomic percent of Fe solutes into Al enables the formation of nanotwinned (nt) columnar grains with high‐density 9R phase in Al(Fe) solid solutions. The nt Al–Fe alloy coatings reach a maximum hardness of ≈5.5 GPa, one of the strongest binary Al alloys ever created. In situ uniaxial compressions show that the nt Al–Fe alloys populated with 9R phase have flow stress exceeding 1.5 GPa, comparable to high‐strength steels. Molecular dynamics simulations reveal that high strength and hardening ability of Al–Fe alloys arise mainly from the high‐density 9R phase and nanoscale grain sizes.
Stable Molecular Diodes Based on π–π Interactions of the Molecular Frontier Orbitals with Graphene Electrodes
Authors: Song Peng , Guerin Sarah , Tan Sherman Jun Rong , Annadata Harshini Venkata , Yu Xiaojiang , Scully Micheál , Han Ying Mei , Roemer Max , Loh Kian Ping , Thompson Damien , Nijhuis Christian A.
Published: January 2018

In molecular electronics, it is important to control the strength of the molecule–electrode interaction to balance the trade‐off between electronic coupling strength and broadening of the molecular frontier orbitals: too strong coupling results in severe broadening of the molecular orbitals while the molecular orbitals cannot follow the changes in the Fermi levels under applied bias when the coupling is too weak. Here, a platform based on graphene bottom electrodes to which molecules can bind via π–π interactions is reported. These interactions are strong enough to induce electronic function (rectification) while minimizing broadening of the molecular frontier orbitals. Molecular tunnel junctions are fabricated based on self‐assembled monolayers (SAMs) of Fc(CH2)11X (Fc = ferrocenyl, X = NH2, Br, or H) on graphene bottom electrodes contacted to eutectic alloy of gallium and indium top electrodes. The Fc units interact more strongly with graphene than the X units resulting in SAMs with the Fc at the bottom of the SAM. The molecular diodes perform well with rectification ratios of 30–40, and they are stable against bias stressing under ambient conditions. Thus, tunnel junctions based on graphene with π–π molecule–electrode coupling are promising platforms to fabricate stable and well‐performing molecular diodes.
Polyethylene‐Glycol‐Mediated Self‐Assembly of Magnetite Nanoparticles at the Liquid/Vapor Interface
Authors: Vaknin David , Wang Wenjie , Islam Farhan , Zhang Honghu
Published: January 2018

It is shown that magnetite nanoparticles (MagNPs) grafted with polyethylene glycol (PEG) self‐assemble and short‐range‐order as 2D films at surfaces of aqueous suspensions by manipulating salt concentrations. Synchrotron X‐ray reflectivity and grazing‐incidence small angle X‐ray scattering studies reveal that K2CO3 induces the migration of the PEG‐MagNPs to the liquid/vapor interface to form a Gibbs layer of monoparticle in thickness. As the salt concentration and/or nanoparticle concentration increase, the surface‐adsorbed nanoparticles become more organized. And further increase in salt concentration leads to the growth of an additional incomplete nanoparticle layer contiguous to the first one at the vapor/liquid interface that remains intact.
Facile On‐Site Detection Based on Reactional Wettability Variation
Authors: Lin Changxu , Xiang Zheng , Song Chen , Lin Youhui , Xu Mengchun , Wang Xuefen , Wu Chenxu , Liu Xiang‐yang
Published: January 2018

A new on‐site detection strategy is developed based on reactional wettability variation (RWV), which is induced by the coordination reaction between azoimidazole (AzoIm) ligands on an electrospun polymer membrane and the analytes. A sensor unit is fabricated by implanting photoresponsive AzoIm ligands on an electrospun polymer membrane. Contact angle of analyte solution droplets on the membrane surface is varied by coordination reaction between ligands and analytes. The response variation of each analyte is influenced by the membrane‐forming polymer and the conformation of AzoIm. Based on these two factors, the sensor is expanded into a sensor array to offer on‐site detection. The principle component analysis is further applied to evaluate the detection performance and influential structural factors of the array on those ions. The differential response it works on results from varied binding constants of ion–AzoIm complexes and pH of the analyte solutions. Moreover, the detection of metal ions is extended to the bioinorganic molecule of hemin in the same mechanism. It is envisioned that the application of the RWV general pattern can open new possibilities for detection.