bluuebunny/crossref_metadata_2025 huggingface dataset:
Listening to the Ancestral Wisdom of Diatomite Cliffs
Authors: Lykke Nina
Published: November 2024

This article focuses on green politics in Denmark, highlighting how mainstream political rhetorics with cruel optimism promote the country as a green world leader, while turning a blind eye to the eco-cides that have formed its landscapes. The primary aim is to critically consider how the terraforming of farmland through ecocidal approaches has been naturalized and normalized as part of national identity-building. A second aim is, affirmatively, to explore whether affected and affecting creative writing and speculative story-telling can be used to counter-act the cruelly optimistic indifference and insensitivity towards the more-than-human world, cultivated through normalization and naturalization. The article uses a vignette methodology. Two vignettes focus on human-human power relations, reflecting on the formation of Danish national identity during modernity. The third vignette shifts the perspective through a writing experiment, telling a speculative-spectrally fictionalized version of Danish history from a more-than-human perspective. A cliff, made by the micro-algae, diatoms, 55 million years ago, performs as the protagonist of a folktale-inspired story about the coming into being of Denmark through series of ecocides. The conclusion reflects on the defamiliarizing effects of the posthuman poetics used in the third vignette’s writing experiment, and compares notes with posthumanist and decolonial scholarship.
Patentes de medicamentos e doenças negligenciadas: a dupla vitimização da pobreza no Brasil
Authors: Domingues Pablo , De Gregori Isabel
Published: November 2024

Este trabalho investiga as consequências do sistema de patente na saúde pública a partir das implicações na produção e desenvolvimento de medicamentos, partindo do objeto de estudo “doenças negligenciadas” centrada no contexto brasileiro. Como método de abordagem, elegeu-se o dedutivo por partir de conceitos e normatizações que envolvem o direito à saúde e à medicamentos, passando pelas implicações econômicas, jurídicas e políticas trazidas pelas patentes para, então, chegar nas doenças negligenciadas e identificar as implicações desse sistema sobre elas. Concluiu-se que sobre as doenças negligenciadas, as patentes de medicamentos produzem um oligopólio das indústrias farmacêuticas que manipulam artificialmente os preços dos medicamentos, trabalham com a escassez de matérias primas somente porque não trazem o lucro desejado e, por consequência, é mantido o status de doença negligenciada em razão do desabastecimento de medicamentos e tratamentos efetivos. Além disso, faz ressurgir doença antes erradicadas ao desabastecer o sistema de saúde pública, gerando uma dupla vitimização da população pobre porque ignoradas pela indústria farmacêutica que não tem interesse na produção de medicamentos para uma população que não terá condições financeiras de comprar o fármaco.
Impuestos globales sobre las emisiones de gases de efecto invernadero: un entretejido democrático entre justicia fiscal y climática
Authors: Tavares Francisco Mata Machado , Gonçalves Carolina Lima
Published: November 2024

El objetivo de la investigación es proponer un impuesto global como desincentivador pigouviano de las emisiones de carbono y para financiar medidas de reparación y generación de alternativas sostenibles para personas excluidas socialmente. Se propone un diseño de política fiscal y ambiental internacional inspirado en la democracia radical, mediante la institucionalización de una autoridad fiscal internacional capaz de recaudar y administrar los impuestos que gravan las emisiones de gases de efecto invernadero. Esta perspectiva incluye una mirada doblemente referenciada en la Nueva Sociología Fiscal y en el neoconstructivismo en el diseño de políticas públicas, y parte de un diálogo crítico con las omisiones político-democráticas en los estudios sobre impuestos globales. La literatura sobre tributación y democracia sugiere que las políticas ambientales y de equidad social financiadas por fondos internacionales son más exitosas si están asociadas a la recaudación de impuestos y sujetas a procesos democráticos e inclusivos. Por lo tanto, se propone un arreglo democrático-participativo para democratizar las relaciones fiscales internacionales y promover la justicia climática. La reforma tributaria reciente en Colombia y propuestas similares en Chile y Brasil pueden servir de inspiración para el diseño de foros democrático-participativos como elementos procesales y sustantivos para auxiliar los debates sobre impuestos a favor de la justicia climática.
Entre o desenvolvimento econômico e a regulação ambiental: participação popular, livre iniciativa e custos do licenciamento ambiental
Authors: Porto Antônio José Maristrello , Diniz Erick Sobral , Franco Paulo Fernando de Mello
Published: November 2024

O presente trabalho tem o intuito de abordar o licenciamento ambiental, questionando o desempenho do modelo institucional disposto pela legislação e implementado pelos órgãos competentes do SISNAMA, no que concerne a questões políticas, custos socioambientais e audiências públicas, comparando-os com as demandas postas pela iniciativa privada. Para tanto, em um primeiro momento expõe-se o ambiente de riscos e incertezas, frente à necessidade de implementação de precaução de modo não só a dimensionar eventuais consequências, a evitar efeitos intergeracionais e danos ambientais irreversíveis, mas também para redimensionar a proteção ambiental em uma relação de custo-benefício. Após, analisa-se a função do poder de polícia na execução da regulação ambiental e sua relação com os custos do licenciamento e o equilíbrio entre o excesso burocrático e a degradação ambiental descomedida. Em seguida, indaga-se sobre as possibilidades de conciliação dos custos socioambientais com a participação popular, em um contexto de excessivas demandas à iniciativa privada. Por fim, analisa-se o projeto de lei 654/15 e a deferência para a administração pública como possível alternativa para a resolução de situações concretas, com adequada participação popular nos processos licenciatórios.
Assemblies, synapse clustering and network topology interact with plasticity to explain structure-function relationships of the cortical connectome
Authors: Ecker András , Egas Santander Daniela , Abdellah Marwan , Alonso Jorge Blanco , Bolaños-Puchet Sirio , Chindemi Giuseppe , Gowri Mariyappan Dhuruva Priyan , Isbister James B , King James Gonzalo , Kumbhar Pramod , Magkanaris Ioannis , Muller Eilif B , Reimann Michael W
Published: November 2024

Synaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have revealed mechanisms and protocols for the induction of plasticity between pairs of neurons, how these synaptic changes are coordinated in biological neuronal networks to ensure the emergence of learning remains poorly understood. Simulation and modeling have emerged as important tools to study learning in plastic networks, but have yet to achieve a scale that incorporates realistic network structure, active dendrites, and multi-synapse interactions, key determinants of synaptic plasticity. To rise to this challenge, we endowed an existing large-scale cortical network model, incorporating data-constrained dendritic processing and multi-synaptic connections, with a calcium-based model of functional plasticity that captures the diversity of excitatory connections extrapolated to
in vivo
-like conditions. This allowed us to study how dendrites and network structure interact with plasticity to shape stimulus representations at the microcircuit level. In our simulations, plasticity acted sparsely and specifically, firing rates and weight distributions remained stable without additional homeostatic mechanisms. At the circuit level, we found plasticity was driven by co-firing stimulus-evoked functional assemblies, spatial clustering of synapses on dendrites, and the topology of the network connectivity. As a result of the plastic changes, the network became more reliable with more stimulus-specific responses. We confirmed our testable predictions in the MICrONS datasets, an openly available electron microscopic reconstruction of a large volume of cortical tissue. Our results quantify at a large scale how the dendritic architecture and higher-order structure of cortical microcircuits play a central role in functional plasticity and provide a foundation for elucidating their role in learning.
CARD8 inflammasome activation during HIV-1 cell-to-cell transmission
Authors: Kulsuptrakul Jessie , Emerman Michael , Mitchell Patrick S
Published: November 2024

Our previous work demonstrated that CARD8 detects HIV-1 infection by sensing the enzymatic activity of the HIV protease, resulting in CARD8-dependent inflammasome activation (Kulsuptrakul et al., 2023). CARD8 recognition of HIV-1 protease activity is conferred by a HIV protease substrate mimic within the CARD8 N-terminus, which when cleaved by HIV protease triggers CARD8 inflammasome activation. Here, we sought to understand CARD8 responses to HIV-1 when the virus is transmitted through cell-to-cell infection from infected cells to target cells via a viral synapse. We observed that cell-to-cell transmission of HIV-1 induces CARD8 inflammasome activation in immortalized cells and primary human monocyte-derived macrophages in a manner that is dependent on viral protease activity and largely independent of the NLRP3 inflammasome. Additionally, to further evaluate the viral determinants of CARD8 sensing, we tested a panel of HIV protease inhibitor resistant clones to establish how variation in HIV protease affects CARD8 activation. We identified mutant HIV-1 proteases that differentially cleave and activate CARD8 compared to wildtype HIV-1, thus indicating that natural variation in HIV protease affects not only the cleavage of the viral Gag-Pol polyprotein but also likely impacts innate sensing and inflammation.
Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice
Authors: Varani Andres P , Mailhes-Hamon Caroline , Sala Romain W , Fouda Sarah , Frontera Jimena L , Léna Clément , Popa Daniela
Published: November 2024

Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.
eIF3 engages with 3’-UTR termini of highly translated mRNAs
Authors: Mestre-Fos Santi , Ferguson Lucas , Trinidad Marena , Ingolia Nicholas T , Cate Jamie HD
Published: November 2024

Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.
Telomere length sensitive regulation of Interleukin Receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment
Authors: Mukherjee Ananda Kishore , Dutta Subhajit , Singh Ankita , Sharma Shalu , Roy Shuvra Shekhar , Sengupta Antara , Chatterjee Megha , Vinayagamurthy Soujanya , Bagri Sulochana , Khanna Divya , Verma Meenakshi , Soni Dristhi , Budharaja Anshul , Bhisade Sagar Kailasrao , Vivekanand  , Perwez Ahmad , George Nija , Faruq Mohammed , Gupta Ishaan , Sabarinathan Radhakrishnan , Chowdhury Shantanu
Published: November 2024

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (Telomeric Repeat binding Factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the
IL1R1
promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like
IL6, IL8
and
TNF
. Further,
IL1R1
expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with
IL1R1
expression. The use of both IL1 Receptor antagonist (IL1RA) and
IL1R1
targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.
PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking
Authors: Forman Thomas E , Sajek Marcin P , Larson Eric D , Mukherjee Neelanjan , Fantauzzo Katherine A
Published: November 2024

Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) plays a critical role in craniofacial development, as mutations in
PDGFRA
are associated with cleft lip/palate in humans and
Pdgfra
mutant mouse models display varying degrees of facial clefting. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during skeletal development in the mouse. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRα signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of
Srsf3
in the murine neural crest lineage results in severe midline facial clefting, due to defects in proliferation and survival of cranial neural crest cells, and widespread alternative RNA splicing (AS) changes. Here, we sought to determine the molecular mechanisms by which Srsf3 activity is regulated downstream of PDGFRα signaling to control AS of transcripts necessary for craniofacial development. We demonstrated via enhanced UV-crosslinking and immunoprecipitation (eCLIP) of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. Moreover, we found that the subset of transcripts that are bound by Srsf3 and undergo AS upon PDGFRα signaling commonly encode regulators of PI3K signaling and early endosomal trafficking. Functional validation studies further confirmed that Srsf3 activity downstream of PDGFRα signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.
Adaptive Integration of Perceptual and Reward Information in an Uncertain World
Authors: Ganesh Prashanti , Cichy Radoslaw M , Schuck Nicolas W , Finke Carsten , Bruckner Rasmus
Published: November 2024

Perceptual uncertainty and salience both impact decision-making, but how these factors precisely impact trial-and-error reinforcement learning is not well understood. Here, we test the hypotheses that (H1) perceptual uncertainty modulates reward-based learning and that (H2) economic decision-making is driven by the value and the salience of sensory information. For this, we combined computational modeling with a perceptual uncertainty-augmented reward-learning task in a human behavioral experiment (
N
= 98). In line with our hypotheses, we found that subjects regulated learning behavior in response to the uncertainty with which they could distinguish choice options based on sensory information (belief state), in addition to the errors they made in predicting outcomes. Moreover, subjects considered a combination of expected values and sensory salience for economic decision-making. Taken together, this shows that perceptual and economic decision-making are closely intertwined and share a common basis for behavior in the real world.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation
Authors: Isbister James B , Ecker András , Pokorny Christoph , Bolaños-Puchet Sirio , Santander Daniela Egas , Arnaudon Alexis , Awile Omar , Barros-Zulaica Natali , Alonso Jorge Blanco , Boci Elvis , Chindemi Giuseppe , Courcol Jean-Denis , Damart Tanguy , Delemontex Thomas , Dietz Alexander , Ficarelli Gianluca , Gevaert Mike , Herttuainen Joni , Ivaska Genrich , Ji Weina , Keller Daniel , King James , Kumbhar Pramod , Lapere Samuel , Litvak Polina , Mandge Darshan , Muller Eilif B , Pereira Fernando , Planas Judit , Ranjan Rajnish , Reva Maria , Romani Armando , Rössert Christian , Schürmann Felix , Sood Vishal , Teska Aleksandra , Tuncel Anil , Van Geit Werner , Wolf Matthias , Markram Henry , Ramaswamy Srikanth , Reimann Michael W
Published: November 2024

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to study
in vivo
. Large-scale, biophysically detailed models offer a tool which can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically-detailed neurons, and 13.2 billion local and mid-range synapses.
In silico
tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome which included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation and investigation.
HØFY-studentenes ressurser og kompetanse i møte med Bachelorstudiet i byggeplassledelse
Authors: Drange Roger , Lier Arne Roar , Sannerud Arne Ronny , Solbakken Atle
Published: November 2024

Høyere yrkesfaglig utdanning har i de senere årene fått oppmerksomhet med blant annet fokus på Fagskolen. Høyskolen for Yrkesfag (HØFY) ble etablert i 2019, og i 2020 ble det første kullet bachelor i byggeplassledelse tatt opp. Høsten 2023 har totalt 235 studenter gjennomført eller gjennomfører studiet ved HØFY. Det er viktig for HØFY som utdanningsinstitusjon å få kjennskap til sine studenter og deres erfaringer og kompetanse. Derfor ble det etablert en spørreundersøkelse som er denne artikkelens empiriske grunnlag. Problemstillingen er todelt, den første er mot hvilke ressurser og kompetanse studentene besitter, og den andre delen retter søkelys på hvilke innsatsfaktorer disse kvalifikasjonene kan være i konstruksjonen av et tredje læringsrom, altså grensesnittet «skole – arbeidsliv». Resultatene fra spørreundersøkelsene dokumenterer at studentene har en rik arbeidserfaring, som lærling, fagarbeider og med ulike lederoppgaver, i tillegg solid formell utdanning. Den andre delen av Problemstillingen diskuterer hvordan og hvorfor studentenes erfaringer og kompetanse kan komme i spill under konstruksjonen av et hybrid læringsrom som en hensiktsmessig læringsarena for denne type studenter.
Effectiveness of Virtual Reality-based Rehabilitation and High-intensity Exercise Program for Total Knee Arthroplasty Patients: A Randomised Controlled Trial
Authors: Nishitha K , Anitha A , Thaheera D
Published: November 2024

Introduction: Progression of articular cartilage loss and wear and strain are the usual causes of Osteoarthritis (OA), sometimes referred to as degenerative joint disease. India had roughly 200,000 knee arthroplasty procedures in 2020 in which nearly 72% were because of OA. Rebuilding the knee joint through knee arthroplasty is a great alternative for treating symptomatic OA in patients who have not responded to conservative treatment. Aim: To determine the effect of Virtual Reality (VR)- based rehabilitation and high-intensity exercise program for Total Knee Arthroplasty (TKA). Materials and Methods: In this double-blinded randomised controlled trial, 36 participants matched the inclusion criteria who underwent Total Knee Replacement (TKR) at the Department of Physiotherapy, Saveetha College of Physiotherapy, SIMATS, Chennai, Tamil Nadu, India. The study was started in the month of October 2023 and ended in January 2024. Then the participants were randomly allotted to an experimental group-VR (n=18) and a conventional group-high-intensity exercises (n=18). Outcome measures used are the Numeric Pain Rating Scale (NPRS) pain scale, knee range of motion, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Timed Up and Go (TUG) test. A paired t-test was utilised to evaluate significant variations between the pre- and post-test measurements. In order to find any meaningful differences between the two groups, an unpaired t-test was employed. Result: The average mean±Standard Deviation (SD) of age and Body Mass Index (BMI) was found to be 51.2±5.2 yearsand 28.3±2.0 kg/m². The experimental group and the conventional group both exhibited notable changes in terms of within-group differences. Numeric Pain Rating Scale (NPRS) significantly showed the same between the groups, but the range of motion showed better output in VR-based rehabilitation than indifferently supporting the pain outcome of the experimental group (p≥0.0001). Balance, gait and functional activities were improved in the experimental group compared to the conventional group and in the VR-based rehabilitation, the functional independence of the patient was achieved in nine weeks compared to the High-intensity (HI) exercises. Conclusion: The VR-based rehabilitation showed better outcomes in pain, range of motion, balance, gait and functional independence than a high-intensity exercise programme.
Multiorgan-dysfunction Secondary to Glyphosate Poisoning: A Case Report
Authors: Karlapudi Pujitha , Pandurangan Viswanathan , Srinivasan Devasena , Joyce Divya
Published: November 2024

Globally, glyphosate is the most widely used non selective broad-spectrum herbicide. The uncoupling of oxidative phosphorylation and polyoxymethylene amine-mediated cardiotoxicity are thought to contribute to glyphosate toxicity. Hereby, the authors presents a case report of 54-year-old male with an alleged history of consuming glyphosate, who experienced complications 48-72 hours after ingestion. These complications included acute kidney injury, corrosive injury to the oesophageal mucosa, cardiotoxicity, and Acute Respiratory Distress Syndrome (ARDS). These are rare but severe manifestations of oral glyphosate-Polyoxyethyleneamine (POEA) poisoning. The patient survived due to aggressive supportive therapy, which included renal replacement therapy, non invasive ventilation, and heart failure management. Since, there is no antidote for glyphosate poisoning, exposure to glyphosate can be fatal, necessitating vigorous supportive therapy. Published data indicate that the use of additional therapies, such as intravenous (i.v.) fat emulsion (20% intralipid, 100 mL) and adsorption haemoperfusion cartridge filters, has had limited success
Valproate-induced Hyperammonaemia in a Bipolar Disorder Patient: A Case Report
Authors: Nair Induja , Kantipudi Suvarna Jyothi
Published: November 2024

Valproate is a widely used mood stabiliser in neurology and psychiatric practice. It can cause rare but serious adverse effects, including hyperammonaemia. Hereby, the authors present a case report of 40-year-old married male diagnosed with bipolar affective disorder, who presented with manic symptoms and subsequently developed hyperammonaemia after the initiation of Sodium Valproate. Despite normal liver function and no history of substance use, the patient exhibited excessive drowsiness and constipation five days after increasing the valproate dosage to 1500 mg/day. Serum ammonia levels were significantly elevated, prompting the cessation of all psychiatric medications and the initiation of lactulose treatment. Over six days, ammonia levels normalised, revealing the underlying manic symptoms. The patient was transitioned to Lithium for mood stabilisation while Valproate was not reintroduced. The case highlights the potential for hyperammonaemia in patients receiving valproate, even in the absence of liver dysfunction. The mechanisms behind this adverse effect may include Carnitine depletion and toxic metabolite accumulation from valproate metabolism. The report underscores the importance of vigilance in monitoring for hyperammonaemia, particularly in patients receiving rapid dose escalations of valproate. Limitations of the report include the absence of serum Valproate levels at the time of hyperammonaemia, which would have aided in understanding the dose-response relationship. It also highlights the need for early detection of hyperammonaemia and appropriate management.
Recent Advances on Polymer Lipid Particles (
PoLP
) in Membrane Protein Research
Authors: de Marcos Lousa Carine , Postis Vincent
Published: July 2018

Membrane proteins (MPs) structure elucidation is of crucial importance as they represent a major target for drug design. However, owing to their high hydrophobicity, MPs are challenging proteins to study. The use of polymer lipid nanoparticles (PoLP) has recently allowed a leap forward in the field of MP research. A wide range of polymers have been successfully used for elucidating the structure of MPs. One polymer in particular, styrene maleic acid (SMA) copolymer, is recently catching a large interest owing to its easy use in detergent‐free membrane solubilisation and the recent successes in purification and stabilising MPs for further biophysical studies.

Key Concepts

SMA copolymers are new tools to purify membrane proteins.

SMA copolymers can solubilise membrane proteins directly without the need of detergents.

Membrane proteins purified in SMALP are stable over time and remain active owing to the retention of native lipids around the proteins.

SMA use limitations include acid pH sensitivity, divalent cations sensitivity and UV absorption.

New polymers (SMA and others) are being engineered to overcome these limitations.
Corporate Strategy
Authors: Brønn Carl , Brønn Peggy Simcic
Published: July 2018

Strategy is a multipurpose concept with many applications. As a noun, it is a field of study and practice concerned with the overall performance of systems, usually human activity systems. As an adjective, it typically modifies nouns denoting common business functions that are generally understood as operational, where adding the word “strategic” has the effect of highlighting their contributions to the long‐term viability of the firm. Strategy implies a high‐level perspective, broader scope, or greater responsibility that contrasts with the tactical or operational levels of the organization. In general, the focus of strategy is on the organization's long‐term direction. This involves defining the scope of its activities, and building and maintaining the resources and capabilities required to support its objectives. A strategy should address how to gain and sustain advantage over competitors in a dynamic and changing business environment.
Metaphors in Organization
Authors: Torp Simon Møberg
Published: July 2018

This entry presents various understandings of, and approaches to, metaphors in organizations. Metaphors arise when, for example, (i) meaning is transferred from a source domain to a target domain, (ii) two domains are blended, or (iii) there is cross‐domain mapping in the conceptual system. Metaphors have been used intentionally both by theorists and researchers to analyze and study organizations, and by consultants and practitioners in the context of problem solving and organizational development. Additionally, metaphors play a crucial role in relation to the actual development of theories of organizations. Inductive and deductive approaches are found within metaphor‐based organizational research, in which metaphors are respectively elicited from or projected onto the organizational reality. Likewise, as regards the form of metaphor research, it is possible to distinguish between discursive and cognitive approaches. Metaphors are perceived both as potentially emancipatory and as a means of concealing and reifying existing power relationships and power structures in organizations.
Electric‐Field‐Assisted Single‐Step In Situ Fabrication and Focal Length Control of Polymeric Convex Lens on Flexible Substrate
Authors: Kim Jonghyun , Shin Dongwoon , Mahmood Tawsif , Chang Jiyoung
Published: July 2018

Here, a simple method for fabricating polymeric convex lens and controlling of its focal length in a single‐step fabrication is presented. The method utilizes electrostatic force to pull the polymer droplet to form the lens, as well as to accelerate the droplet to control the curvature of the lens simultaneously. Lenses with various diameter (ranging from 0.75 to 4.5 mm) and curvature are sequentially fabricated at the preprogrammed position on a dielectric and flexible substrate. Since a transparent dielectric flexible film is employed as a target substrate, not only the electrical short circuit in the process is prevented but also high optical transmittance is secured with superior mechanical bendability which allows transformation of the lens into a positive single‐axis meniscus. To show the functionality, the lenses are integrated into a microscope for a teleconverter, fluidic tubing for a magnifier, laser exposing for a concentrator, and LED bulb encapsulating as a light diffuser. The presented method with extremely simple fabrication step with focal length control is expected to be directly applied to a wide range of applications.
All‐Dielectric Metalattice with Enhanced Toroidal Dipole Response
Authors: Sayanskiy Andrey , Danaeifar Mohammad , Kapitanova Polina , Miroshnichenko Andrey E.
Published: July 2018

A novel type of all‐dielectric metalattice is proposed and experimentally demonstrated, which supports broadband dominant toroidal dipole response. The unit cell consists of four rectangular bars made of dielectric materials of moderate contrast. By performing multipole decomposition it is found that toroidal dipole response is dominant over a wide frequency range. The correlation between the toroidal dipole response and longitudinal electric field component is also shown. By using this feature, as well as direct near‐field mapping, the broadband toroidal dipole response of such metalattice is experimentally verified. Since the unit cell exhibits C4 rotational symmetry this response is shown to be polarization independent.
Targeting the Achilles Heel of Zika Virus and Other Emerging Viral Pathogens
Authors: Jackman Joshua A. , Cho Nam‐Joon
Published: July 2018

Viruses are a leading cause of infectious diseases and represent one of the world's biggest global health problems. The continual appearance of new and reemerging viruses exceeds our capacity to provide effective medical solutions, as highlighted by the recent Zika epidemic. Herein, the authors discuss how unconventional approaches might lead to innovations in antiviral drug development that would address this outstanding need. In particular, the case of Zika virus is analyzed and the authors suggest that a materials science and engineering perspective might revolutionize antiviral drug development. Zika virus and related viruses possess a lipid membrane envelope that is an Achilles heel because it is necessary for viral function and there is a high barrier for mutations to evolve there. The development of antiviral drugs, such as certain membrane‐active peptides, to selectively target the lipid membrane envelope would represent an entirely new therapeutic approach. Such efforts could be aided by engineering approaches to design and characterize promising drug candidates that work against multiple viruses. Looking forward, there is excellent potential to develop new therapeutic strategies that target the Achilles heel of Zika virus and other emerging viral pathogens.
A Lithium–Sulfur Cell Based on Reversible Lithium Deposition from a Li2S Cathode Host onto a Hostless‐Anode Substrate
Authors: Nanda Sanjay , Gupta Abhay , Manthiram Arumugam
Published: July 2018

The development of lithium–sulfur batteries necessitates a thorough understanding of the lithium‐deposition process. A novel full‐cell configuration comprising an Li2S cathode and a bare copper foil on the anode side is presented here. The absence of excess lithium allows for the realization of a truly lithium‐limited Li–S battery, which operates by reversible plating and stripping of lithium on the hostless‐anode substrate (copper foil). Its performance is closely tied to the efficiency of lithium deposition, generating valuable insights on the role and dynamic behavior of lithium anode. The Li2S full cell shows reasonable capacity retention with a Coulombic efficiency of 96% over 100 cycles, which is a tremendous improvement over that of a similar lithium‐plating‐based full cell with LiFePO4 cathodes. The exceptional robustness of the Li2S system is attributed to an intrinsic stabilization of the lithium‐deposition process, which is mediated by polysulfide intermediates that form protective Li2S and Li2S2 regions on the deposited lithium. Combined with the large improvements in energy density and safety by the elimination of a metallic lithium anode, the stability and electrochemical performance of the lithium‐plating‐based Li2S full cell establish it as an important trajectory for Li–S battery research, focusing on practical realization of reversible lithium anodes.
Impact of emergency physicians competent in severe trauma management, surgical techniques, and interventional radiology on trauma management
Authors: Otsuka Hiroyuki , Sato Toshiki , Sakurai Keiji , Aoki Hiromichi , Yamagiwa Takeshi , Iizuka Shinichi , Inokuchi Sadaki
Published: July 2018

Aim

Despite recent advancements in trauma management following introduction of interventional radiology (IVR) and damage‐control strategies, challenges remain regarding optimal use of resources for severe trauma.

Methods

In October 2014, we implemented a trauma management system comprising emergency physicians competent in severe trauma management, surgical techniques, and IVR. To evaluate this system, of 5,899 trauma patients admitted to our hospital from January 2011 to January 2018, we selected 107 patients with severe trauma (injury severity score ≥ 16) who presented with persistent hypotension (two or more systolic blood pressure measurements <90 mmHg), regardless of primary resuscitation. Patients were divided according to the date of admission: Conventional (January 2011–September 2014) or Current (October 2014–January 2018). The primary end‐point was in‐hospital mortality. Secondary end‐points included time from arrival to start of surgery/IVR.

Results

There were 59 patients in the Conventional group and 48 in the Current group. Although patients in the Current group were more severely ill compared with those in the Conventional group, mortality in the Current group was significantly lower (Conventional 64.4% versus Current 41.7%, P = 0.019), especially among patients whose first intervention was IVR (Conventional 75.0% versus Current 28.6%, P = 0.001). Time from arrival to initiation of surgery/IVR was shorter in the Current group (Conventional 71.5 [53.8–130.8] min versus Current 41.0 [26.0–58.5] min, P < 0.0001).

Conclusions

This trauma management system based on emergency physicians competent not only in severe trauma management, but also surgical techniques and IVR, could improve outcomes in patients with severe multiple lethal trauma.
Generating DNA sequence data with limited resources for molecular biology: Lessons from a barcoding project in Indonesia
Authors: Dean Gillian H. , Asmarayani Rani , Ardiyani Marlina , Santika Yessi , Triono Teguh , Mathews Sarah , Webb Campbell O.
Published: July 2018

The advent of the DNA sequencing age has led to a revolution in biology. The rapid and cost‐effective generation of high‐quality sequence data has transformed many fields, including those focused on discovering species and surveying biodiversity, monitoring movement of biological materials, forensic biology, and disease diagnostics. There is a need to build capacity to generate useful sequence data in countries with limited historical access to laboratory resources, so that researchers can benefit from the advantages offered by these data. Commonly used molecular techniques such as DNA extraction, PCR, and DNA sequencing are within the reach of small laboratories in many countries, with the main obstacles to successful implementation being lack of funding and limited practical experience. Here we describe a successful approach that we developed to obtain DNA sequence data during a small DNA barcoding project in Indonesia.
Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex–Mediated Activation of the NLRP3 Inflammasome
Authors: Shin Min Sun , Kang Youna , Wahl Elizabeth R. , Park Hong‐Jai , Lazova Rossitza , Leng Lin , Mamula Mark , Krishnaswamy Smita , Bucala Richard , Kang Insoo
Published: July 2018

Objective

High‐expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity of systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing U1 snRNP and anti–U1 snRNP antibodies, which are found in patients with SLE, activates the NLRP3 inflammasome, comprising NLRP3, ASC, and procaspase 1, in human monocytes, leading to the production of interleukin‐1β (IL‐1β). This study was undertaken to investigate the role of the snRNP immune complex in up‐regulating the expression of MIF and its interface with the NLRP3 inflammasome.

Methods

MIF, IL‐1β, NLRP3, caspase 1, ASC, and MIF receptors were analyzed by enzyme‐linked immunosorbent assay, Western blotting, quantitative polymerase chain reaction, and cytometry by time‐of‐flight mass spectrometry (CytoF) in human monocytes incubated with or without the snRNP immune complex. MIF pathway responses were probed with the novel small molecule antagonist MIF098.

Results

The snRNP immune complex induced the production of MIF and IL‐1β from human monocytes. High‐dimensional, single‐cell CytoF analysis established that MIF regulates activation of the NLRP3 inflammasome, including findings of a quantitative relationship between MIF and its receptors and IL‐1β levels in the monocytes. MIF098, which blocks MIF binding to its cognate receptor, suppressed the production of IL‐1β, the up‐regulation of NLRP3, which is a rate‐limiting step in NLRP3 inflammasome activation, and the activation of caspase 1 in snRNP immune complex–stimulated human monocytes.

Conclusion

The U1 snRNP immune complex is a specific stimulus of MIF production in human monocytes, with MIF having an upstream role in defining the inflammatory characteristics of activated monocytes by regulating NLRP3 inflammasome activation and downstream IL‐1β production. These findings provide mechanistic insight and a therapeutic rationale for targeting MIF in subgroups of lupus patients, such as those classified as high genotypic MIF expressers or those with anti‐snRNP antibodies.
Assembled Nanocomplex for Improving Photodynamic Therapy through Intraparticle Fluorescence Resonance Energy Transfer
Authors: Cao Hongqian , Qi Yanfei , Yang Yang , Wang Lei , Sun Jiaheng , Li Yue , Xia Jiarui , Wang Hao , Li Junbai
Published: July 2018

In recent years, one of main obstacles in a photodynamic therapy (PDT) process has been that most photosensitizers for PDT are excited by visible light with limited penetrating ability; thus most applications of PDT are for superficial treatments. One of the methods to increase the treatment depth is to introduce a two‐photon‐active technique into PDT, known as TP‐PDT. The difficulty here is to obtain photosensitizers with a large enough two‐photon absorption cross‐section. In this work, an organic nanocomplex, composed of the two‐photon nanoaggregate as the core and photosensitizer as the shell, has been constructed. Photosensitizers could be excited indirectly through a fluorescence resonance energy transfer (FRET) mechanism after the two‐photon core was excited by a two‐photon laser. The FRET efficiency was extremely high, owing to sufficient energy donors and stable energy acceptors. In this way, a photosensitizer could induce two‐photon toxicity for improving the treatment depth in PDT. The nanocomplexes were prepared through a molecular assembly method, which avoided complicated reactions for synthesizing two‐photon photosensitizers. The assembly method would expand the selection of photosensitizers and two‐photon dyes, and endow traditional photosensitizers with a larger two‐photon absorption cross‐section for TP‐PDT.
Enantioselective Liquid–Liquid Extraction of Underivatized Amino Acids with Simple Chiral Aminophenyl‐Aldehyde
Authors: Chen Qian , Jin Yingji , Huang Haofei , Su Zhishan , Kim Seong Kyu , Kim Kwan Mook
Published: July 2018

The derivative of aminophenyl‐aldehyde with an asymmetric carbon and an uryl group, (S)‐2, was synthesized. The combination of (S)‐2 and aliquat‐336 in CDCl3 extracted underivatized amino acids in water layer by imine formation with enantioselectivities of 12/1 for Phe, 13/1 for Val, and 12/1 for Leu, which are comparable with those of previously reported binaphthol‐based extractor (S)‐1. The enantioselectivities of (S)‐2 is remarkable considering the low molecular weight compared to (S)‐1. Density functional theory computations and experimental data demonstrate that imine bond is strengthened by resonance‐assisted hydrogen bond with the nearby NH group.
Identifying new clotting factor XIa inhibitors in virtual high‐throughput screens using PCA‐GA‐SVM models and signature
Authors: Chen Jonathan J. , Schmucker Lyndsey N. , Visco Donald P.
Published: July 2018

Blood Clotting Factor XI is an important actor in the clotting mechanism: it activates downstream zymogen involved in the clotting process. It can be targeted for activation or inhibition depending on treatment goals to enhance or inhibit clotting. In terms of antithrombosis treatment, Factor XI has emerged as a promising target to focus on. In this work, an iterative virtual high‐throughput screening pipeline was proposed that can supplement current efforts to find inhibitors. The first iteration identified 11 compounds to test with 3 active for a hit‐rate of 27.3%. The second iteration of the pipeline identified another 11 compounds to test with 7 active for a hit‐rate of 63.6%. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1553–1565, 2018
Milling performance of waxy wheat and wild‐type wheat using two laboratory milling methods
Authors: Xu Bin , Mense Andrew , Ambrose Kingsly , Graybosch Robert , Shi Yong‐Cheng
Published: July 2018

Background and objectives

Flour and starch from waxy wheat (Triticum aestivum L) have unique properties such as high water‐holding capacity, low pasting temperature, low syneresis, and high resistance to retrogradation. However, the milling performance of waxy wheat was not well documented. In this study, the milling quality of a waxy wheat (Mattern) was evaluated by comparing its flour yield, chemical composition, flow properties, and particle size distribution with that of two wild‐type hard red winter (HRW) wheats (Wesley and Everest) using two laboratory milling methods. The effects of moisture level and tempering time on milling behavior for the waxy wheat (Mattern) were examined and compared with that of wild‐type wheat.

Findings

Waxy wheat (Mattern) seemed to require more moisture during tempering than wild‐type wheats to achieve a similar drop in SKCS hardness. For Mattern, the overall grain hardness drop was minimal when tempering to moisture contents below 17.5%. When the tempering moisture content increased from 13% to 17.5%, the flour yield increased, but decreased after 17.5% moisture content. Tempering Mattern to 16% and higher resulted in a higher bran yield compared with shorts yield, although the yield of the shorts from Mattern was significantly greater than that of the shorts from both wild‐type wheats. The flour yield of Mattern was 65.1%, which was significantly lower than that of both wild‐type wheats (73.1% for Wesley and 72.2% for Everest).

Conclusions

At the same moisture content (16%), the hardness of the waxy wheat (Mattern) kernel decreased at a slower rate than the wild‐type wheat during tempering for 48 hr. The flour yield of the waxy wheat (Mattern) was significantly lower than that of wild‐type wheat. Mattern flour was less free‐flowing and more adhesive than the wild‐type HRW flour, mainly due to its smaller particle size and higher fat content.

Significance and novelty

Higher optimal tempering moisture was needed to mill the waxy wheat (Mattern), and the yield of waxy wheat flour was maximized when the kernels were tempered at 17.5% moisture for 24 hr.
Congenital multiple coronary arteriovenous fistulas
Authors: Lacalzada‐Almeida Juan , García‐Niebla Javier , Izquierdo‐Gómez María M. , Marí‐López Belén , Laynez‐Cerdeña Ignacio , Bosa‐Ojeda Francisco
Published: July 2018

Key Clinical Message

Coronary arteriovenous fistulas are congenital or acquired abnormalities characterized by abnormal communication between the coronary circulation and cardiac chambers or other vessels. Frequently, patients are asymptomatic and their diagnosis can be carried out incidentally by echocardiography. Knowing the echocardiographic findings characteristic of this malformation will prevent the diagnosis from going unnoticed.