bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses
Authors: Moriyama Miyu , Koshiba Takumi , Ichinohe Takeshi
Published: October 2019

Cytosolic mitochondrial DNA (mtDNA) activates cGAS-mediated antiviral immune responses, but the mechanism by which RNA viruses stimulate mtDNA release remains unknown. Here we show that viroporin activity of influenza virus M2 or encephalomyocarditis virus (EMCV) 2B protein triggers translocation of mtDNA into the cytosol in a MAVS-dependent manner. Although influenza virus-induced cytosolic mtDNA stimulates cGAS- and DDX41-dependent innate immune responses, the nonstructural protein 1 (NS1) of influenza virus associates with mtDNA to evade the STING-dependent antiviral immunity. The STING-dependent antiviral signaling is amplified in neighboring cells through gap junctions. In addition, we find that STING-dependent recognition of influenza virus is essential for limiting virus replication in vivo. Our results show a mechanism by which influenza virus stimulates mtDNA release and highlight the importance of DNA sensing pathway in limiting influenza virus replication.
HCMV-encoded US7 and US8 act as antagonists of innate immunity by distinctively targeting TLR-signaling pathways
Authors: Park Areum , Ra Eun A. , Lee Taeyun A. , Choi Hyun jin , Lee Eunhye , Kang Sujin , Seo Jun-Young , Lee Sungwook , Park Boyoun
Published: October 2019

The mechanisms by which many human cytomegalovirus (HCMV)-encoded proteins help the virus to evade immune surveillance remain poorly understood. In particular, it is unknown whether HCMV proteins arrest Toll-like receptor (TLR) signaling pathways required for antiviral defense. Here, we report that US7 and US8 as key suppressors that bind both TLR3 and TLR4, facilitating their destabilization by distinct mechanisms. US7 exploits the ER-associated degradation components Derlin-1 and Sec61, promoting ubiquitination of TLR3 and TLR4. US8 not only disrupts the TLR3-UNC93B1 association but also targets TLR4 to the lysosome, resulting in rapid degradation of the TLR. Accordingly, a mutant HCMV lacking the US7-US16 region has an impaired ability to hinder TLR3 and TLR4 activation, and the impairment is reversed by the introduction of US7 or US8. Our findings reveal an inhibitory effect of HCMV on TLR signaling, which contributes to persistent avoidance of the host antiviral response to achieve viral latency.
Actin-microtubule interplay coordinates spindle assembly in human oocytes
Authors: Roeles Johannes , Tsiavaliaris Georgios
Published: October 2019

Mammalian oocytes assemble a bipolar acentriolar microtubule spindle to segregate chromosomes during asymmetric division. There is increasing evidence that actin in the spindle interior not only participates in spindle migration and positioning but also protects oocytes from chromosome segregation errors leading to aneuploidy. Here we show that actin is an integral component of the meiotic machinery that closely interacts with microtubules during all major events of human oocyte maturation from the time point of spindle assembly till polar body extrusion and metaphase arrest. With the aid of drugs selectively affecting cytoskeleton dynamics and transiently disturbing the integrity of the two cytoskeleton systems, we identify interdependent structural rearrangements indicative of a close communication between actin and microtubules as fundamental feature of human oocytes. Our data support a model of actin-microtubule interplay that is essential for bipolar spindle assembly and correct partitioning of the nuclear genome in human oocyte meiosis.
Microsatellite genotypes of the South African Cape vulture, Gyps coprotheres
Authors: Kleinhans Courtneë , Willows-Munro Sandi
Published: October 2019

Across the globe, vulture species are experiencing major population declines. A key factor for the long-term persistence of these endangered species is the maintenance of genetic diversity patterns within wild populations. The datasets presented in this descriptor includes microsatellite genotypes of 605 Cape vultures (Gyps coprotheres) drawn from across the southern African distribution of the species. Microsatellites are useful in quantifying genetic diversity at the population level. Populations of the endangered Cape vulture are currently monitored by conservation agencies and the data presented here can be used as an important baseline for future population genetic monitoring.
Introducing the first whole genomes of nationals from the United Arab Emirates
Authors: AlSafar Habiba S. , Al-Ali Mariam , Elbait Gihan Daw , Al-Maini Mustafa H. , Ruta Dymitr , Peramo Braulio , Henschel Andreas , Tay Guan K.
Published: October 2019

Whole Genome Sequencing (WGS) provides an in depth description of genome variation. In the era of large-scale population genome projects, the assembly of ethnic-specific genomes combined with mapping human reference genomes of underrepresented populations has improved the understanding of human diversity and disease associations. In this study, for the first time, whole genome sequences of two nationals of the United Arab Emirates (UAE) at >27X coverage are reported. The two Emirati individuals were predominantly of Central/South Asian ancestry. An in-house customized pipeline using BWA, Picard followed by the GATK tools to map the raw data from whole genome sequences of both individuals was used. A total of 3,994,521 variants (3,350,574 Single Nucleotide Polymorphisms (SNPs) and 643,947 indels) were identified for the first individual, the UAE S001 sample. A similar number of variants, 4,031,580 (3,373,501 SNPs and 658,079 indels), were identified for UAE S002. Variants that are associated with diabetes, hypertension, increased cholesterol levels, and obesity were also identified in these individuals. These Whole Genome Sequences has provided a starting point for constructing a UAE reference panel which will lead to improvements in the delivery of precision medicine, quality of life for affected individuals and a reduction in healthcare costs. The information compiled will likely lead to the identification of target genes that could potentially lead to the development of novel therapeutic modalities.
Simple and large-scale chromosomal engineering of mouse zygotes via in vitro and in vivo electroporation
Authors: Iwata Satoru , Nakadai Hitomi , Fukushi Daisuke , Jose Mami , Nagahara Miki , Iwamoto Takashi
Published: October 2019

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has facilitated dramatic progress in the field of genome engineering. Whilst microinjection of the Cas9 protein and a single guide RNA (sgRNA) into mouse zygotes is a widespread method for producing genetically engineered mice, in vitro and in vivo electroporation (which are much more convenient strategies) have recently been developed. However, it remains unknown whether these electroporation methods are able to manipulate genomes at the chromosome level. In the present study, we used these techniques to introduce chromosomal inversions of several megabases (Mb) in length in mouse zygotes. Using in vitro electroporation, we successfully introduced a 7.67 Mb inversion, which is longer than any previously reported inversion produced using microinjection-based methods. Additionally, using in vivo electroporation, we also introduced a long chromosomal inversion by targeting an allele in F1 hybrid mice. To our knowledge, the present study is the first report of target-specific chromosomal inversions in mammalian zygotes using electroporation.
Depletion of CD40 on CD11c+ cells worsens the metabolic syndrome and ameliorates hepatic inflammation during NASH
Authors: Aarts Suzanne , Reiche Myrthe , den Toom Myrthe , Gijbels Marion , Beckers Linda , Gerdes Norbert , Lutgens Esther
Published: October 2019

The co-stimulatory CD40-CD40L dyad plays a central role in fine-tuning immune reactions, including obesity-induced inflammation. Genetic ablation of CD40L reduced adipose tissue inflammation, while absence of CD40 resulted in aggravated metabolic dysfunction in mice. During obesity, CD40 expressing CD11c+ dendritic cells (DC) and macrophages accumulate in adipose tissue and liver. We investigated the role of CD40+CD11c+ cells in the metabolic syndrome and nonalcoholic steatohepatitis (NASH). DC-CD40-ko mice (CD40fl/flCD11ccre) mice were subjected to obesity or NASH. Obesity and insulin resistance were induced by feeding mice a 54% high fat diet (HFD). NASH was induced by feeding mice a diet containing 40% fat, 20% fructose and 2% cholesterol. CD40fl/flCD11ccre mice fed a HFD displayed increased weight gain, increased adipocyte size, and worsened insulin resistance. Moreover, CD40fl/flCD11ccre mice had higher plasma and hepatic cholesterol levels and developed profound liver steatosis. Overall, regulatory T cell numbers were decreased in these mice. In NASH, absence of CD40 on CD11c+ cells slightly decreased liver inflammation but did not affect liver lipid accumulation. Our experiments suggest that CD40 expressing CD11c+ cells can act as a double-edged sword: CD40 expressing CD11c+ cells contribute to liver inflammation during NASH but are protective against the metabolic syndrome via induction of regulatory T cells.
Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling
Authors: El Zein Rami M. , Soria Audrey H. , Golib Dzib Jose Felipe , Rickard Amanda J. , Fernandes-Rosa Fabio L. , Samson-Couterie Benoit , Giscos-Douriez Isabelle , Rocha Angélique , Poglitsch Marko , Gomez-Sanchez Celso E. , Amar Laurence , Ghyselinck Norbert B. , Benecke Arndt , Zennaro Maria-Christina , Boulkroun Sheerazed
Published: October 2019

Primary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. Inactivation of Rarα in mice led to significant structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA.
Biodegradable Surgical Staple Composed of Magnesium Alloy
Authors: Amano Hizuru , Hanada Kotaro , Hinoki Akinari , Tainaka Takahisa , Shirota Chiyoe , Sumida Wataru , Yokota Kazuki , Murase Naruhiko , Oshima Kazuo , Chiba Kosuke , Tanaka Yujiro , Uchida Hiroo
Published: October 2019

Currently, surgical staples are composed of non–biodegradable titanium (Ti) that can cause allergic reactions and interfere with imaging. This paper proposes a novel biodegradable magnesium (Mg) alloy staple and discusses analyses conducted to evaluate its safety and feasibility. Specifically, finite element analysis revealed that the proposed staple has a suitable stress distribution while stapling and maintaining closure. Further, an immersion test using artificial intestinal juice produced satisfactory biodegradable behavior, mechanical durability, and biocompatibility in vitro. Hydrogen resulting from rapid corrosion of Mg was observed in small quantities only in the first week of immersion, and most staples maintained their shapes until at least the fourth week. Further, the tensile force was maintained for more than a week and was reduced to approximately one-half by the fourth week. In addition, the Mg concentration of the intestinal artificial juice was at a low cytotoxic level. In porcine intestinal anastomoses, the Mg alloy staples caused neither technical failure nor such complications as anastomotic leakage, hematoma, or adhesion. No necrosis or serious inflammation reaction was histopathologically recognized. Thus, the proposed Mg alloy staple offers a promising alternative to Ti alloy staples.
Improving water retention capacity of an aeolian sandy soil with feldspathic sandstone
Authors: Zhang Lu , Han Jichang
Published: October 2019

The Mu Us sandy land in China’s Shaanxi Province faces a critical water shortage, with its aeolian sandy soil endangering the regional eco-environment. Here we investigated the effects of feldspathic sandstone on water retention in an aeolian sandy soil from the Mu Us sandy land. Feldspathic sandstone and aeolian sandy soil samples were mixed at different mass ratios of 0:1 (control), 1:5 (T1), 1:2 (T2), and 1:1 (T3). Soil-water characteristic curves were determined over low- to medium-suction (1–1000 kPa) and high-suction (1000–140 000 kPa) ranges, by centrifuge and water vapor equilibrium methods, respectively. Results showed that the addition of feldspathic sandstone modified the loose structure of the aeolian sandy soil mainly consisting of sand grains. The van Genuchten model described well the soil-water characteristic curves of all four experimental soils (R2-values > 0.97). Soil water content by treatment was ranked as T2 > T3 > T1 > control at the same low matric suction (1–5 kPa), but this shifted to T2 > T1 > T3 > control at the same medium- to high-suction (5–140 000 kPa). T2 soil had the largest saturated water content, with a relatively high water supply capacity. This soil (T2) also had the largest field capacity, total available water content, and permanent wilting coefficient, which were respectively 17.82%, 11.64%, and 23.11% higher than those of the control (P-values < 0.05). In conclusion, adding the feldspathic sandstone in an appropriate proportion (e.g., 33%) can considerably improve the water retention capacity of aeolian sandy soil in the study area.
Worry and metacognitions as predictors of the development of anxiety and paranoia
Authors: Sun Xiaoqi , So Suzanne H. , Chan Raymond C. K. , Chiu Chui-De , Leung Patrick W. L.
Published: October 2019

Recent studies have shown that worry and related negative metacognitions are characteristic in generalized anxiety and paranoia respectively. However, most of these studies did not take into account common co-occurrence of anxiety and paranoia, and longitudinal modelling of the role of worry and metacognitions on the development of anxiety and paranoia is rare. The current study aimed at examining the bidirectional longitudinal relationship between anxiety and paranoia, as well as the importance of worry and metacognitions in the development of these symptoms. Our validated sample consisted of 2291 participants recruited from universities, among whom 1746 participants (76.21%) completed online questionnaires at baseline and at one year, reporting levels of anxiety, paranoia, worry, and negative metacognitions. Structural equation modeling analyses, followed by path comparisons, revealed that anxiety and paranoia mutually reinforced each other over time. Negative metacognitions, rather than worry itself, were contributive to the development of both symptoms over time. Negative metacognitions showed bi-directional relationships with anxiety over the time period assessed and showed uni-directional relationships with paranoia. Clinical implications of our findings are discussed.
Soft mobile robot inspired by animal-like running motion
Authors: Park Tongil , Cha Youngsu
Published: October 2019

There is a considerable demand for legged robots with exploring capabilities such as passing through narrow pathways. Soft robots can provide a solution for such applications. Here, we propose a soft legged mobile robot with bimorph piezoelectric main body and pre-curved piezoelectric legs. We experimentally demonstrate the performance of the soft mobile robot. The mobile robot can move 70% of the body length per second. In addition, we investigate physical mechanisms behind the locomotion of the mobile robot using a numerical simulation. Interestingly, the mobile robot generates an animal-like running motion. We find that the amplitude difference of the legs, depending on the leg activation condition, may affect the performance of the robot. We also confirm that the soft mobile robot can maintain the movement under impulsive shock owing to its flexibility.
The photocurrent generated by photon replica states of an off-resonantly coupled dot-cavity system
Authors: Abdullah Nzar Rauf , Tang Chi-Shung , Manolescu Andrei , Gudmundsson Vidar
Published: October 2019

Transport properties of a quantum dot coupled to a photon cavity are investigated using a quantum master equation in the steady-state regime. In the off-resonance regime, when the photon energy is smaller than the energy spacing between the lowest electron states of the quantum dot, we calculate the current that is generated by photon replica states as the electronic system is pumped with photons. Tuning the electron-photon coupling strength, the photocurrent can be enhanced by the influences of the photon polarization, and the cavity-photon coupling strength of the environment. We show that the current generated through the photon replicas is very sensitive to the photon polarization, but it is not strongly dependent on the average number of photons in the environment.
Meso/macroscopically multifunctional surface interfaces, ridges, and vortex-modified anode/cathode cuticles as force-driven modulation of high-energy density of LIB electric vehicles
Authors: Khalifa H. , El-Safty S. A. , Reda A. , Shenashen M. A. , Selim M. M. , Alothman O. Y. , Ohashi N.
Published: October 2019

Modulation of lithium-ion battery (LIB) anodes/cathodes with three-dimensional (3D) topographical hierarchy ridges, surface interfaces, and vortices promotes the power tendency of LIBs in terms of high-energy density and power density. Large-scale meso-geodesics offer a diverse range of spatial LIB models along the geodetically shaped downward/upward curvature, leading to open-ended movement gate options, and diffusible space orientations. Along with the primary 3D super-scalable hierarchy, the formation of structural features of building block egress/ingress, curvature cargo-like sphere vehicles, irregularly located serrated cuticles with abundant V-undulated rigidness, feathery tube pipe conifers, and a band of dagger-shaped needle sticks on anode/cathode electrode surfaces provides high performance LIB modules. The geodetically-shaped anode/cathode design enables the uniqueness of all LIB module configurations in terms of powerful lithium ion (Li+) movement revolving in out-/in- and up-/downward diffusion regimes and in hovering electron density for high-speed discharge rates. The stability of built-in anode//cathode full-scale LIB-model meso-geodesics affords an outstanding long-term cycling performance. The full-cell LIB meso-geodesics offered 91.5% retention of the first discharge capacity of 165.8 mAhg−1 after 2000 cycles, Coulombic efficiency of ~99.6% at the rate of 1 C and room temperature, and high specific energy density of ≈119 Wh kg−1. This LIB meso-geodesic module configuration may align perfectly with the requirements of the energy density limit mandatory for long-term EV driving range and the scale-up commercial manufactures.
Highly improved acetone oxidation activity over mesoporous hollow nanospherical MnxCo3−xO4 solid solutions
Authors: Wang Jinguo , Zhang Chi , Yang Shuaifeng , Liang Hao , Men Yong
Published: October 2019

Mesoporous hollow nanospherical MnxCo3−xO4 solid solutions synthesized by a facile solvothermal alcoholysis have been developed to catalyze acetone oxidation for the first time.
Coexistence of Cu(ii) and Cu(i) in Cu ion-doped zeolitic imidazolate frameworks (ZIF-8) for the dehydrogenative coupling of silanes with alcohols
Authors: Dai Yan , Xing Peng , Cui Xiaoqin , Li Zhihong , Zhang Xianming
Published: October 2019

Coexistence of Cu(ii) and Cu(i) in Cu ion doped ZIF-8 nanocrystals for dehydrogenative coupling.
Protonation and electrochemical properties of a bisphosphide diiron hexacarbonyl complex bearing amino groups on the phosphide bridge
Authors: Shimamura Takehiko , Maeno Yuki , Kubo Kazuyuki , Kume Shoko , Greco Claudio , Mizuta Tsutomu
Published: October 2019

A bisphosphide-bridged diiron hexacarbonyl complex with NEt2groups on the phosphide bridge was synthesized to examine a new proton relay system.
The added value of a zebrafish embryo–larval model in the assessment of wastewater tertiary treatments
Authors: García-Cambero J. P. , Beltrán F. J. , Encinas A. , Rivas F. J. , Oropesa A. L.
Published: October 2019

Photocatalytic oxidation for 120 min of a wastewater doped with 9 pharmaceuticals at 10 mg L−1 each gave an innocuous effluent for zebrafish embryo development.
Flaxseed oil supplementation improves intestinal function and immunity, associated with altered intestinal microbiome and fatty acid profile in pigs with intrauterine growth retardation
Authors: Che Lianqiang , Zhou Qiang , Liu Yan , Hu Liang , Peng Xie , Wu Cheng , Zhang Ruinan , Tang Jiayong , Wu Fali , Fang Zhengfeng , Lin Yan , Xu Shengyu , Feng Bin , Li Jian , Jiang Pingping , Wu De , Chen Daiwen
Published: October 2019

Flaxseed-supplemented diet could improve intestinal function and immunity of both IUGR and NBW pigs, associated with the altered gut microbiome and mucosal fatty acid profile.
Primary amine catalyzed diastereo- and enantioselective Michael reaction of thiazolones and α,β-unsaturated ketones
Authors: Lu Min , Li Hong , Zou Chuncheng , Li Jianchang , Liu Chengyu , Sun Maolin , Ma Yueyue , Cheng Ruihua , Ye Jinxing
Published: October 2019

Organocatalytic asymmetric Michael reactions between thiazolones and α,β-unsaturated ketones were developed. By using primary amine catalysts, the products were obtained with good to excellent yields and stereoselectivities.
Synthesis and photochromism of some mono and bis (thienyl) substituted oxathiine 2,2-dioxides
Authors: Aiken Stuart , Gabbutt Christopher D. , Heron B. Mark , Rice Craig R. , Zonidis Dimitrios
Published: October 2019

The addition of sulfenes to substituted enaminoketones, followed by a facile Cope elimination, provides access to a novel series of photochromic dithienylethenes containing a 1,2-oxathiine 2,2-dioxide core.
Preparation of copper phthalocyanine/SiO2 composite particles through simple, green one-pot wet ball milling in the absence of organic dispersants
Authors: Chen Zhijie , Wang Xianghong , Lang Wenchang , Qi Dongming
Published: October 2019

Submicrometer copper phthalocyanine (CuPc)/SiO2 composite particles were prepared through a simple one-pot wet ball-milling process under acidic condition without using any organic surfactant.
Light-enabled metal-free pinacol coupling by hydrazine
Authors: Qiu Zihang , Pham Hanh D. M. , Li Jianbin , Li Chen-Chen , Castillo-Pazos Durbis J. , Khaliullin Rustam Z. , Li Chao-Jun
Published: October 2019

A light-driven pinacol coupling protocol without any metals, but with N2H4as a clean non-metallic hydrogen-atom-transfer (HAT) reductant was described.
Cysteine-to-lysine transfer antibody fragment conjugation
Authors: Forte Nafsika , Benni Irene , Karu Kersti , Chudasama Vijay , Baker James R.
Published: October 2019

Site-selective antibody fragment conjugation is achieved by using a disulfide bond to ‘hook’ and deliver thioester acylating agents to specific lysines.
Poly(dimethylsiloxane)/graphene oxide composite sponge: a robust and reusable adsorbent for efficient oil/water separation
Authors: Zhao Jiajun , Chen Hongyun , Ye Huijian , Zhang Bingpan , Xu Lixin
Published: October 2019

The development of polymer sponges with large adsorption capacity, high oil/water selectivity and mechanical stability is an effective strategy for the separation of oil from oil-polluted water.
Post-Genomic Partnership for Chemistry and Biology: 16 November 2001
Authors: Burd Gary
Published: October 2019

Biology and Chemistry Departments have traditionally occupied separate buildings on campus -- at one time in the not too distant past, few universities managed to encourage mingling. A one-day symposium, organized by the UKLSC and RSC, aimed to address some of the issues involved in convincing biologists that chemistry is invaluable, and vice versa. The presentations demonstrated how a mixture of disciplines can achieve impressive results in the new post-genomic proteomic era.
Second Rothamsted International BioMarket: 7–9 November 2001
Authors: Atkin Roger
Published: October 2019

The Biochemical Society was one of the sponsors of the Second Rothamsted International BioMarket on ‘Bioproducts from Plants and Microbes’ which was held at IACR-Rothamsted on 7–9 November 2001. The aim of this biopartnering event was to bring together those interested in commercializing products and services based in plants and microbes. It was attended by research entrepreneurs from the private and public sectors, industrial liaison officers, intellectual property experts, financiers and others interested in the emerging business global opportunities for bioproducts. Some 23 countries were represented.
Muriel Wheldale Onslow (1880–1932): pioneer plant biochemist
Authors: Rayner-Canham Marelene , Rayner-Canham Geoffrey
Published: October 2019

The British biochemist Muriel Wheldale Onslow was one of only two genetics researchers in the first decade of the 20th century who performed plant breeding experiments and also investigated the corresponding chemistry of flower pigments of the plants (the other being Erwin Bauer in Germany)1. J.B.S. Haldane used her research to conclude that genes controlled the formation of large molecules, such as pigment molecules2.
Plastic fantastic!: Body Worlds
Authors: Burd Gary
Published: October 2019

Love him or loathe him, Professor Günther von Hagens has set the scientific and art worlds alight with his controversial exhibition of plastinated humans stripped of their skins. The exhibition has made it to the unglamourous Old Truman Brewery in London's East End, and was sending shockwaves through the media, and even Parliament, before it even opened. Set in thought-provoking positions, are the pieces there for education or are they an abomination?
Portland Press Limited: the year 2001 in review
Authors: Turner AJ
Published: October 2019

I am delighted to report that 2001 was an extremely successful year for the Biochemical Society's publishing subsidiary, Portland Press Limited, particularly as my previous report predicted a significant increase in turnover -- it feels very good to have been right! The company achieved a profit on ordinary activities after taxation of £602244 (compared with £337419 in 2000), which was gifted to the Biochemical Society to enable it to carry out its charitable objectives. This excellent performance is a direct result of the investment that was made in information technology (IT) systems and to the successful re-organization of the Portland Customer Services Centre (PCSC), which took place in 2000.
The musical brain: A meeting of minds
Authors: Burd Gary
Published: October 2019

The Royal Institution's special summer event this year was a day-long public forum on one of the most rapidly developing fields of human research. The examination of the relationship between music and brain-function has been going on in earnest for around a decade. Several leading experts in the field gave presentations, and following the forum, there were two evening performances by the National Youth Orchestra and the Orpheus Centre. The event was sponsored by the International Foundation for Music Research and the Kohn Foundation. Baroness Susan Greenfield demonstrated the role of the Royal Institution to the audience by showing the mixture of disciplines present at the public forum, as both scientists, musicians and members of the public come together to discuss science.
Paper weight?: Electronic lab notebooks
Authors: Bavins Terry
Published: October 2019

The ongoing pressure to find the next blockbuster drug is felt nowhere more keenly than in the area of drug discovery, in which ever-increasing volumes of data need to be thoroughly analysed and likely candidates must be rapidly identified and patented. IT is already essential to the generation and processing of raw data in most drugdiscovery labs (the huge forward leaps in genomics, for example, would be unthinkable without it), and this was the area where the need for automation was initially most obvious and pressing.
Past times: Traffic in the rear-view mirror
Authors: Lucocq John
Published: October 2019

When I was a lad, the adage that “cells are not simply bags full of enzymes” was already popular in biology, and how true it turned out to be. We now know that eukaryotes comprise cellular compartments whose integrity and composition is maintained by specific mechanisms, including the membrane traffic between membrane-bound organelles. So what attracts cell biologists to the challenge of membrane traffic? One reason may be the complexity in composition and spatio-temporal dynamics -- a complexity that manifests itself in the sheer beauty of the physical forms of the trafficking organelles. Another motivation may be the simple question of how complex mixtures of substances can be moved around selectively in membrane-bound vesicles while maintaining the compositional integrity of organelles. Whatever the attraction, it is clear that the full molecular inventory of traffic machinery will be known soon, and we stand now on the threshold of a deeper understanding. It is therefore a good time to look at what has been achieved so far. Interestingly, the focus of membrane trafficking research has come full circle. Initially, discrete organelles with specialized functions were described and then came a mass of molecular information. Now, we are back to the organelles, trying to work out how they are built and how they function in a dynamic way. As in any story of science, the road to discovery has been crucially dependent on clever insights, married with technical developments at both molecular and atomic resolution.
Ancient enzymology?: Ribozymes
Authors: Lilley David M.J.
Published: October 2019

Ribozymes are RNA molecules that act like enzymes to accelerate chemical reactions. They may be relics of an ancient ‘RNA world’, where RNA performed both informational and catalytic functions before proteins took over the latter role. As enzymes, RNA molecules are rather poor prospects, with a paucity of functional groups, yet in a limited set of reactions they achieve respectable rate enhancements. Explaining this is a significant challenge to the biological chemist, and the area has seldom been free from controversy. Some general conclusions are, however, now emerging. RNA achieves a lot from a very limited resource, from which some general insights into biocatalysis may emerge.
Single-molecule enzymology: What can it tell us?
Authors: Bagshaw Clive R.
Published: October 2019

In the last decade, several methods have been developed to measure enzyme activity at the level of a single enzyme molecule. This represents a considerable technical feat, but what does it allow us to learn about enzymes? Here, the basic principles are reviewed to show that new forms of heterogeneity in activity may be revealed and evidence gained for rare states that would otherwise be swamped in bulk assays.
Slaves to the rhythm: Oscillations, cycling and the pace of life
Authors: Rudolf Fabian , Wehrle Franziska , Staiger Dorothee
Published: October 2019

Plants, as sessile organisms, are forced to take advantage of the limited availability of sunlight, their most important resource. Not surprisingly, many aspects of physiology and development are therefore organized by an endogenous chronometer in plants. This so-called ‘circadian’ clock imposes a 24-hour rhythm on metabolic reactions and physiological processes to optimally align them with the environmental light-dark cycle1.
Central and peripheral oscillators in mammals: A guided tour through a network of clocks
Authors: Guillaumond Fabienne , Cermakian Nicolas
Published: October 2019

For decades, the circadian system of animals was viewed as a single or a few centralized structures driving all overt physiological circadian rhythms. Recent data have questioned this view and have revealed a much more complex and dynamic picture. We now know that circadian oscillators are also present in many different tissues and constitute part of a hierarchical circadian system. In this article, we describe this multi-oscillator system that constitutes the basis for the variety of physiological rhythms.
Joined up government?: Supporting Excellence in the Science Base
Authors: Withnall Mike
Published: October 2019

In late 2003, the biosciences community was horrified by a proposal from the Higher Education Funding Council for England (HEFCE) in a consultation paper on the future funding method for teaching, to split the price band B for science, engineering and technology subjects into two sub-groups. All bioscience disciplines would be in the B2 sub-group, which would have its resource rate cut by 7.4%, while those in B1 would see an increase of 15.7%.
New enzymes, new mechanisms?: DNA repair by recombination in the Archaea
Authors: Bolt Edward L. , Allers Thorsten
Published: October 2019

DNA repair by homologous recombination is highly accurate, since it uses an intact DNA strand to guide repair of its damaged homologue. This article focuses on two key steps in recombination: unwinding of strands by repair helicases, and annealing of homologous strands by strand-exchange enzymes.
Keeping data readable: Ensuring the long-term viability of analytical data
Authors: Duckworth James
Published: October 2019

Several trends in the life and analytical sciences industry are changing the way in which scientists both conduct experiments and share data. Large companies are consolidating, becoming more global and extending the enterprise to include partners and Contract Research Organizations (CROs).
RNAi and cancer research: The path to a cure?
Authors: Downward Julian
Published: October 2019

RNAi, a natural mechanism for silencing gene expression, holds enormous potential as a tool for blocking the function of selected proteins. It is proving invaluable in basic cancer research and also has potential as a therapeutic strategy. Cancer Research UK is exploiting RNAi to study gene function across the genome.
Seeing is believing: Microscopy in RNAi research
Authors: Wright Colin
Published: October 2019

RNA interference (RNAi) is, arguably, one of the most significant medical breakthroughs of recent years. The ability of RNAi to silence genes provides scientists with a highly specific new tool for investigating gene and protein function. Not only can it be used to explore the complex relationships between genes, proteins and disease, but it also offers the promise of new therapeutics targeting disease-causing genes. In this article, we investigate how microscopy can help researchers visualize and monitor processes in this growing research field.
Location, location, location…: Property strategy for biotech companies
Authors: Sylvester Martin
Published: October 2019

The global biotech industry is outperforming market expectations and by 2005, biotech-derived products are predicted to account for £96 billion of worldwide output, a 43% increase on its current level.
Quality Assurance can be applied to fundamental research: Supporting Excellence in the Science Base
Authors: Robins Margaret M.
Published: October 2019

Quality Assurance (QA) has a bad press in research circles. Fundamental researchers tend to consider that experienced scientists do not need any controls beyond their own integrity. This article attempts to show how QA can be applied even to the most original and basic research areas, and that there are benefits to the introduction of a formal system, provided all personnel are involved in the aspects that affect them.
Cholera: the killer from the deep: A paradigm for waterborne disease
Authors: Colwell Rita R.
Published: October 2019

The current international attention to the importance of combating infectious diseases can provide the opportunity for a multidisciplinary approach that joins medicine with many other scientific and technological disciplines. Science and technology are major forces that have the potential to balance the world's inequities. The connection between cholera and the environment provides a paradigm for this perspective.
Message from the cell's powerhouse: Mitochondrial signalling and redox therapeutics
Authors: Landar Aimee L. , Zmijewski Jaroslaw W. , Oh Joo-Yeun , Darley-Usmar Victor M.
Published: October 2019

Some of the earliest studies in bioenergetics described a ‘leak’ of electrons from the mitochondrial respiratory chain to oxygen, with the resulting formation of the simple one-electron product, superoxide. Several lines of evidence led to the idea that this process is pathological. For example, formation of superoxide, and its dismutation product hydrogen peroxide, from the mitochondrion was enhanced by mitochondrial poisons and hyperoxia. Since these early beginnings, studies in the redox cell signalling field have shown that these same reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), serve as signalling molecules in both physiological and pathological situations. These small molecules can act through several mechanisms, including the ability to act as reversible agonists for receptors.
Pharmaceutical industries: do they prefer treatment to cure?
Authors: Mittra James
Published: October 2019

Despite the emergence of novel life-science-based approaches to drug discovery and development and the unprecedented growth of new companies and research organizations competing in the healthcare sector, the industry continues to be dominated by the marketing of small-molecule ‘blockbuster’ therapies developed by large multinationals. The hope that ‘genomics’ would shift the focus from the treatment of symptoms associated with disease to the prevention or cure of many debilitating illnesses has yet to translate into reality. The question is whether traditional pharmaceutical companies simply prefer treatment to cure and, if so, where must society look to ensure that the best science is translated into the most innovative, effective and beneficial clinical products.
A field on fire: The biochemistry of mad cows
Authors: Brown David R.
Published: October 2019

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.
Fungal prions: When proteins turn into genes
Authors: Malato Laurent , Saupe Sven J.
Published: October 2019

Prions are infectious proteic particles devoid of nucleic acids that can cause devastating neurological disorders in mammals. Prions have also been identified in simpler organisms, namely unicellular yeasts and filamentous fungi. These fungal prions represent valuable model systems because they are safe to handle and, compared with mammalian prions, easier to study. In this article, we summarize the basic characteristics of the fungal prions and attempt to describe how their discovery has affected and expanded the prion concept.
Politics and science: an impossible relationship?
Authors: MP Ian Gibson
Published: October 2019

For those outside the Westminster circle, the political machinery behind national politics remains an impenetrable mystery. There is much chicanery surrounding the decision-making process, which often has an impact on policy. You can ask, for example, how evidence is used and whether it is really taken into account. One more minor mystery for many has been the decision to remove me as Chair of the Science and Technology committee. And so, at the request of the Executive Editor of this publication and at the risk of sounding egotistical or, as one reader of the journal Science and Public Affairs indirectly put it, a ‘whinger’, I will attempt to unravel the mysteries that were at work when the chairmanships of the committees were decided, and by so doing, examine the tenuous relationship between politics and science.
The key to success for school science?: The new Key Stage4 curriculum and the changes to science GCSEs
Authors: Baker Hannah
Published: October 2019

“Science will remain compulsory at Key Stage 4 and it remains our firm expectation that at least 80% of students should do at least two science GCSEs.” Government White Paper, age 14–19 Education and Skills, 22 March 2005.
Biochemical Journal -- the first 100 years online
Authors: Kiley Robert , Fishel Martha , Myers Carol
Published: October 2019

As a result of a collaborative project between the Wellcome Trust, the Joint Information Systems Committee (JISC), the US National Library of Medicine (NLM) and Portland Press, the entire archive of the Biochemical Journal -- from 1906 to date -- is now freely available online on both PubMed Central® (PMC) and the Biochemical Journal websites. This article provides the background to the project, as well as highlighting some of the value-added features that the online version offers to the clinician, researcher and medical historian.
A world out there: Teaching the scientists of tomorrow
Authors: Baker Hannah
Published: October 2019

Many fascinating projects, articles, organizations and events exist to enrich science education, research and the lives of all involved. These efforts complement scientific research and, if you know how to use them or get involved, they provide a voice to everyone and crystallize the enthusiasm and passions of scientists the world over.
Protein–carbohydrate interactions: At the heart of biochemistry
Authors: Sharon Nathan
Published: October 2019

Proteins that possess the ability to bind carbohydrates specifically and reversibly abound in nature, being present in all living organisms, from viruses to humans. Their interactions with their ligands are the basis of a myriad of biological processes, both normal and pathological1–3 (Table 1). The high selectivity required for these interactions is provided by a specific stereochemical fit between complementary molecules, the protein on the one hand and the carbohydrate on the other. This concept has its origins in the lock-and-key hypothesis, introduced by Emil Fischer at the end of the 19th Century to explain the specificity of interactions between enzymes (he studied glycosidases) and their substrates (carbohydrates), i.e. between molecules in solution. In time it was extended to describe the interactions of cells with soluble molecules and with other cells.
Raman optical activity: A new light on proteins, carbohydrates and glycoproteins
Authors: Barron Laurence D.
Published: October 2019

The core techniques of structural biology, namely X-ray crystallography and multidimensional NMR, are often not applicable to many important samples due to fundamental experimental problems, such as the lack of suitable crystals in the X-ray case or excessive size or flexibility for NMR. Carbohydrates and glycoproteins are especially challenging in this respect. The novel technique of vibrational ROA (Raman optical activity), which combines the advantages of vibrational spectroscopy with the extra sensitivity to three-dimensional structure of chiroptical methods such as CD (circular dichroism), has much promise for studying a large range of biomolecules, from the smallest to the largest, in aqueous solution. Among other things, it is capable of providing structural information about both the polypeptide and the carbohydrate structure of intact glycoproteins and should become an indispensable spectroscopy tool for glycobiology.
The trap hypothesis: α2 and protease inhibition
Authors: Salvesen Guy S. , Murphy Gillian , Nagase Hideaki
Published: October 2019

In the 1970s, the Strangeways Laboratory in Cambridge consisted of a small number of groups collectively focused on the mechanisms of pathological connective-tissue damage. One of these groups, headed by Alan Barrett, was breaking ground on the destruction of the protein components of the matrix and was therefore heavily involved in identifying and categorizing newly emerging types of tissue-degrading enzymes. These enzymes, which Alan Barrett urges scientists to call peptidases, are also commonly called proteases or proteinases*. In the early 1970s, there were about 100 described human peptidases, a reasonable sampling of the 500–600 now known in humans in the post-genomic age. Approximately 2% of the human genome encodes peptidases, and roughly 1% encodes proteins with the ability to inhibit these enzymes. As the peptidases developed different catalytic mechanisms to solve the problem of cleaving the notoriously stable peptide bond, so the families of protease inhibitors acquired distinct strategies to regulate peptidase action. The strategies are usually directed towards blocking the peptidase active site directly or, less commonly, by allosteric mechanisms. But perhaps the most bizarre mechanism is that performed by members of the protein clan exemplified by the human protein 2-macroglobulin (α2).
Young researchers find their VoYS
Authors: Downey Frances
Published: October 2019

Sense About Science has never been short of enthusiasm from the young research scientists who we have met through our Voice of Young Science (VoYS) programme, which isn't surprising when our mission is to promote good science. Our young researchers want to be part of our VoYS network because they want to challenge bad science when they see it and also promote good science. They also appreciate the support and help that we, and the other young scientists on the network, give them. They are not a lone voice, but part of a much bigger community of young researchers who want to make a difference and proactively engage the public and the media.
Tired out: Biochemical explanations of physical and mental fatigue
Authors: Newsholme Eric A.
Published: October 2019

Physical fatigue is common, complex and controversial and it is hard to define. The best definition is the inability to maintain power output, for example, to maintain the pace of running, the duration of dancing or circuit training. For many years, the cause of fatigue was the province of the physiologist, but now the biochemist has taken over. Fatigue is caused by changes within the muscle ( peripheral fatigue) or within the brain (central fatigue). The latter occurs when the maximal effort that can be achieved voluntarily is less than that which can be achieved when the muscle is stimulated directly through the motor nerve.
Getting hooked: Morphine tolerance
Authors: Bailey Chris
Published: October 2019

Morphine acts on the Gi/Go-coupled -opioid receptor (MOR). The cellular mechanisms underlying tolerance to morphine are poorly understood but research has focused on desensitization and trafficking of MORs. Surprisingly, different agonists at the MOR elicit desensitization by entirely different cellular mechanisms.
Why aren't white coats sexy?: Science and Society
Authors: Rohn Jennifer
Published: October 2019

All single scientists have probably experienced that crucial turning point at a cocktail party: the moment your attractive and intrigued conversational partner asks, “So, what you do?”