bluuebunny/crossref_metadata_2025 huggingface dataset:
Functions for S. cerevisiae Swd2p in 3′ end formation of specific mRNAs and snoRNAs and global histone 3 lysine 4 methylation
Authors: DICHTL BERNHARD , AASLAND REIN , KELLER WALTER
Published: May 2004

The Saccharomyces cerevisiae WD-40 repeat protein Swd2p associates with two functionally distinct multiprotein complexes: the cleavage and polyadenylation factor (CPF) that is involved in pre-mRNA and snoRNA 3′ end formation and the SET1 complex (SET1C) that methylates histone 3 lysine 4. Based on bioinformatic analysis we predict a seven-bladed β-propeller structure for Swd2p proteins. Northern, transcriptional run-on and in vitro 3′ end cleavage analyses suggest that temperature sensitive swd2 strains were defective in 3′ end formation of specific mRNAs and snoRNAs. Protein–protein interaction studies support a role for Swd2p in the assembly of 3′ end formation complexes. Furthermore, histone 3 lysine 4 di-and tri-methylation were adversely affected and telomeres were shortened in swd2 mutants. Underaccumulation of the Set1p methyltransferase accounts for the observed loss of SET1C activity and suggests a requirement for Swd2p for the stability or assembly of this complex. We also provide evidence that the roles of Swd2p as component of CPF and SET1C are functionally independent. Taken together, our results establish a dual requirement for Swd2p in 3′ end formation and histone tail modification.
Multiple functions for the invariant AGC triad of U6 snRNA
Authors: HILLIKER ANGELA K. , STALEY JONATHAN P.
Published: May 2004

The invariant AGC triad of U6 snRNA plays an essential, unknown role in splicing. The triad has been implicated in base-pairing with residues in U2, U4, and U6. Through a genetic analysis in S. cerevisiae, we found that most AGC mutants are suppressed both by restoring pairing with U2, supporting the significance of U2/U6 helix Ib, and by destabilizing U2 stem I, indicating that this stem regulates helix Ib formation. Intriguingly, one of the helix Ib base pairs is required specifically for exon ligation, raising the possibility that the entirety of helix Ib is required only for exon ligation. We also found that U4 mutations that reduce complementarity in U4 stem I enhance U2-mediated suppression of an AGC mutant, suggesting that U4 stem I competes with the AGC-containing U4/U6 stem I. Implicating an additional, essential function for the triad, three triad mutants are refractory to suppression—even by simultaneous restoration of pairing with U2, U4, and U6. An absolute requirement for a purine at the central position of the triad parallels an equivalent requirement in a catalytically important AGC triad in group II introns, consistent with a role for the AGC triad of U6 in catalysis.
Implementing a Production Schedule at LKAB's Kiruna Mine
Authors: Kuchta Mark , Newman Alexandra , Topal Erkan
Published: May 2004

LKAB's Kiruna Mine, located in northern Sweden, produces about 24 million tons of iron ore yearly using an underground mining method known as sublevel caving. To efficiently run the mills that process the iron ore, the mine must deliver planned quantities of three ore types. We used mixed-integer programming to schedule Kiruna's operations, specifically, which production blocks to mine and when to mine them to minimize deviations from monthly planned production quantities while adhering to operational restrictions. These production schedules save costs compared to schedules produced manually by meeting desired production quantities more closely and reducing employee time spent on preparing schedules.
Functional Imaging of Working Memory after 24 Hr of Total Sleep Deprivation
Authors: Chee Michael W. L. , Choo Wei Chieh
Published: May 2004

The neurobehavioral effects of 24 hr of total sleep deprivation (SD) on working memory in young healthy adults was studied using functional magnetic resonance imaging. Two tasks, one testing maintenance and the other manipulation and maintenance, were used. After SD, response times for both tasks were significantly slower. Performance was better preserved in the more complex task. Both tasks activated a bilateral, left hemisphere-dominant frontal-parietal network of brain regions reflecting the engagement of verbal working memory. In both states, manipulation elicited more extensive and bilateral (L>R) frontal, parietal, and thalamic activation. After SD, there was reduced blood oxygenation level-dependent signal response in the medial parietal region with both tasks. Reduced deactivation of the anterior medial frontal and posterior cingulate regions was observed with both tasks. Finally, there was disproportionately greater activation of the left dorsolateral prefrontal cortex and bilateral thalamus when manipulation was required. This pattern of changes in activation and deactivation bears similarity to that observed when healthy elderly adults perform similar tasks. Our data suggest that reduced activation and reduced deactivation could underlie cognitive impairment after SD and that increased prefrontal and thalamic activation may represent compensatory adaptations. The additional left frontal activation elicited after SD is postulated to be task dependent and contingent on task complexity. Our findings provide neural correlates to explain why task performance in relatively more complex tasks is better preserved relative to simpler ones after SD.
Multiple Reference Frames for Motion in the Primate Cerebellum
Authors: Shaikh Aasef G. , Meng Hui , Angelaki Dora E.
Published: May 2004

Knowledge of body motion through space is necessary for spatial orientation, self-motion perception, and postural control. Yet, sensory afferent signals may not directly provide such information to the brain. Because motion detected by the vestibular end organs is encoded in a head-fixed frame of reference, a coordinate transformation is thus required to encode body motion. In this study, we investigated whether cerebellar motion-sensitive neurons encode the translation of the body through space. We systematically changed both the direction of motion relative to the body and the static orientation of the head relative to the trunk. The activities of motion-sensitive neurons in the most medial of the deep cerebellar nuclei, the rostral fastigial nucleus, were compared with those in the brainstem vestibular nuclei. We found a distributed representation of reference frames for motion in the rostral fastigial nucleus, in contrast to cells in the vestibular nuclei, which primarily encoded motion in a head-fixed reference frame. This differential representation of motion-related information implies potential differences in the functional roles of these areas.
Contribution of AMPA, NMDA, and GABAAReceptors to Temporal Pattern of Postsynaptic Responses in the Inferior Colliculus of the Rat
Authors: Wu Shu Hui , Ma Chun Lei , Kelly Jack B.
Published: May 2004

The central nucleus of the inferior colliculus (ICC) is a major site of synaptic interaction in the central auditory system. To understand how ICC neurons integrate excitatory and inhibitory inputs for processing temporal information, we examined postsynaptic responses of ICC neurons to repetitive stimulation of the lateral lemniscus at 10-100 Hz in rat brain slices. The excitatory synaptic currents mediated by AMPA and NMDA receptors and the inhibitory current mediated by GABAAreceptors were pharmacologically isolated and recorded by whole-cell patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and GABAAreceptor-mediated IPSCs were similar and much faster than those of NMDA receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a rate of 10-100 Hz but showed response depression during the course of repetitive stimulation. GABAAIPSCs could also follow stimulus pulses over this frequency range but showed depression at low rates and facilitation at higher rates. NMDA EPSCs showed facilitation and temporal summation in response to repetitive stimulation, which was most pronounced at higher rates of stimulation. GABAAinhibition suppressed activation of NMDA receptors and reduced both the degree of AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The results indicate that GABAAreceptor-mediated inhibition plays a crucial role in maintaining the balance of excitation and inhibition and in allowing ICC neurons to process temporal information more precisely.
Traumatic Axonal Injury Induces Proteolytic Cleavage of the Voltage-Gated Sodium Channels Modulated by Tetrodotoxin and Protease Inhibitors
Authors: Iwata Akira , Stys Peter K. , Wolf John A. , Chen Xiao-Han , Taylor Andrew G. , Meaney David F. , Smith Douglas H.
Published: May 2004

We demonstrated previously that dynamic stretch injury of cultured axons induces structural changes and Ca2+influx modulated by tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (NaChs). In the present study, we evaluated potential damage to the NaCh α-subunit, which can cause noninactivation of NaChs. In addition, we explored the effects of pre-injury and post-injury treatment with TTX and protease inhibition on proteolysis of the NaCh α-subunit and intra-axonal calcium levels ([Ca2+]i) over 60 min after trauma. After stretch injury, we found that [Ca2+]i continued to increase in untreated axons for at least 60 min. We also observed that the III-IV intra-axonal loop of the NaCh α-subunit was proteolyzed between 5 and 20 min after trauma. Pre-injury treatment of the axons with TTX completely abolished the posttraumatic increase in [Ca2+]i and proteolysis of the NaCh α-subunit. In addition, both pre-injury and post-injury inhibition of protease activity attenuated long-term increases in [Ca2+]i as well as mitigating degradation of the NaCh α-subunit. These results suggest a unique “feed-forward” deleterious process initiated by mechanical trauma of axons. Na+influx through NaChs resulting from axonal deformation triggers initial increases in [Ca2+]i and subsequent proteolysis of the NaChα-subunit. In turn, degradation of the α-subunit promotes persistent elevations in [Ca2+]i, fueling additional pathologic changes. These observations may have important implications for developing therapeutic strategies for axonal trauma.
The Population Response of A- and C-Fiber Nociceptors in Monkey Encodes High-Intensity Mechanical Stimuli
Authors: Slugg Robert M. , Campbell James N. , Meyer Richard A.
Published: May 2004

The peripheral neural mechanism of pain to mechanical stimuli remains elusive. C-fiber nociceptors do not appear to play a major role in mechanical pain sensation, because the stimulus-response function of mechanically sensitive C-fiber nociceptors to punctate mechanical stimuli applied to the most sensitive region in the receptive field (the hot spot) reaches a plateau at force levels insufficient to produce pain in humans. However, studies at the hot spot give an incomplete understanding of the inputs of nociceptors to the spinal cord. To estimate how the population of nociceptors responds to a punctate stimulus, it is necessary to know how the response varies with the position within the receptive field. For A-fiber and C-fiber nociceptors, we systemically measured the response to a 100 μm wide blade stimulus as a function of position in the receptive field at different force levels. Highly reproducible receptive field response maps that contained multiple peaks and valleys were obtained. Some peaks were only 100 μm wide. As force increased, the response and width of the peaks increased, the response in valleys increased, and new peaks appeared. The averaged response across the map provides an estimate of the population response and was found to increase monotonically with force over a large stimulus range for both A-fiber and C-fiber nociceptors. These data provide evidence that both C-fiber and A-fiber nociceptors may encode high-intensity mechanical stimuli.
Adult Bone Marrow Stromal Cells in the Embryonic Brain: Engraftment, Migration, Differentiation, and Long-Term Survival
Authors: Muñoz-Elias Guillermo , Marcus Akiva J. , Coyne Thomas M. , Woodbury Dale , Black Ira B.
Published: May 2004

We recently differentiated adult rat and human bone marrow stromal cells (MSCs) into presumptive neurons in cell culture. To determine whether the MSCs assume neuronal functionsin vivo, we now characterize for the first time engraftment, migration, phenotypic expression, and long-term survival after infusion into embryonic day 15.5 (E15.5) rat ventriclesin utero. By E17.5, donor cells formed discrete spheres in periventricular germinal zones, suggesting preferential sites of engraftment. The cells expressed progenitor vimentin and nestin but not mature neuronal markers. By E19.5, a subset assumed elongated migratory morphologies apposed to radial nestin-positive fibers running through the cortical white matter and plate, suggesting migration along radial glial processes. Cells remaining in germinal zones extended long, vimentin-positive fibers into the parenchyma, suggesting that the MSCs generated both migratory neurons and guiding radial glia. Consistent with this suggestion, >50% of cultured mouse MSCs expressed the neuroprecursor/radial glial protein RC2. From E19.5 to postnatal day 3, MSCs populated distant areas, including the neocortices, hippocampi, rostral migratory stream, and olfactory bulbs. Whereas donor cells confined to the subventricular zone continued to express nestin, cells in the neocortex and midbrain expressed mature neuronal markers. The donor cells survived for at least 2 months postnatally, the longest time examined. Confocal analysis revealed survival of thousands of cells per cubic millimeter in the frontal cortex and olfactory bulb at 1 month. In the cortex and bulb, 98.6 and 77.3% were NeuN (neuronal-specific nuclear protein) positive, respectively. Our observations suggest that transplanted adult MSCs differentiate in a regionally and temporally specific manner.
Astrocyte Glutamate Transporters Regulate Metabotropic Glutamate Receptor-Mediated Excitation of Hippocampal Interneurons
Authors: Huang Yanhua H. , Sinha Saurabh R. , Tanaka Kohichi , Rothstein Jeffrey D. , Bergles Dwight E.
Published: May 2004

Clearance of extracellular glutamate is essential for limiting the activity of metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the relative contribution of transporters found in neuronal and glial membranes to this uptake is poorly understood. Hippocampal interneurons located at the oriens-alveus border express mGluR1α, a metabotropic glutamate receptor that regulates excitability and synaptic plasticity. To determine which glutamate transporters are essential for removing glutamate at these excitatory synapses, we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM) interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly depolarized to allow Ca2+entry before stimulation. Selective inhibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihydrokainate increased the amplitude of these responses approximately threefold, indicating that these transporters compete with mGluRs for synaptically released glutamate. However, inhibition of all glutamate transporters with TBOA (dl-threo-b-benzyloxyaspartic acid) increased mGluR1 EPSCs >15-fold, indicating that additional transporters also shape activation of these receptors. To identify these transporters, we examined mGluR1 EPSCs in mice lacking GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for excitatory amino acid carrier; EAAT3). A comparison of responses recorded from wild-type and transporter knock-out mice revealed that the astroglial glutamate transporters GLT-1 and GLAST, but not the neuronal transporter EAAC1, restrict activation of mGluRs in O-LM interneurons. Transporter-dependent potentiation of mGluR1 EPSCs led to a dramatic increase in interneuron firing and enhanced inhibition of CA1 pyramidal neurons, suggesting that acute or prolonged disruption of transporter activity could lead to changes in network activity as a result of enhanced interneuron excitability.
Mechanism of Activity-Dependent Downregulation of the Neuron-Specific K-Cl Cotransporter KCC2
Authors: Rivera Claudio , Voipio Juha , Thomas-Crusells Judith , Li Hong , Emri Zsuzsa , Sipilä Sampsa , Payne John A. , Minichiello Liliana , Saarma Mart , Kaila Kai
Published: May 2004

GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein expression in CA1 pyramidal neurons, which leads to a reduced capacity for neuronal Cl-extrusion. This effect is mediated by endogenous BDNF acting on tyrosine receptor kinase B (TrkB), with down-stream cascades involving both Shc/FRS-2 (src homology 2 domain containing transforming protein/FGF receptor substrate 2) and PLCγ (phospholipase Cγ)-cAMP response element-binding protein signaling. The plasmalemmal KCC2 has a very high rate of turnover, with a time frame that suggests a novel role for changes in KCC2 expression in diverse manifestations of neuronal plasticity. A downregulation of KCC2 may be a general early response involved in various kinds of neuronal trauma.
Targeted Deletion of the Kynurenine Aminotransferase II Gene Reveals a Critical Role of Endogenous Kynurenic Acid in the Regulation of Synaptic Transmission viaα7 Nicotinic Receptors in the Hippocampus
Authors: Alkondon Manickavasagon , Pereira Edna F. R. , Yu Ping , Arruda Emerson Z. , Almeida Luis E. F. , Guidetti Paolo , Fawcett William P. , Sapko Michael T. , Randall William R. , Schwarcz Robert , Tagle Danilo A. , Albuquerque Edson X.
Published: May 2004

It has been postulated that endogenous kynurenic acid (KYNA) modulates α7*nicotinic acetylcholine receptor (nAChR) and NMDA receptor activities in the brain.a To test this hypothesis, α7*nAChR and NMDA receptor functions were studied in mice with a targeted null mutation in the gene encoding kynurenine aminotransferase II (mKat-2-/-mice), an enzyme responsible for brain KYNA synthesis. At 21 postnatal days,mKat-2-/-mice had lower hippocampal KYNA levels and higher spontaneous locomotor activity than wild-type (WT) mice. At this age, α7*nAChR activity induced by exogenous application of agonists to CA1 stratum radiatum interneurons was ∼65% higher inmKat-2-/-than WT mice. Binding studies indicated that the enhanced receptor activity may not have resulted from an increase in α7*nAChR number. In 21-d-oldmKat-2-/-mice, endogenous α7*nAChR activity in the hippocampus was also increased, leading to an enhancement of GABAergic activity impinging onto CA1 pyramidal neurons that could be reduced significantly by acute exposure to KYNA (100 nM). The activities of GABAAand NMDA receptors in the interneurons and of α3β4*nAChRs regulating glutamate release onto these neurons were comparable betweenmKat-2-/-and WT mice. By 60 d of age, KYNA levels and GABAergic transmission in the hippocampus and locomotor activity were similar betweenmKat-2-/-and WT mice. Our findings that α7*nAChRs are major targets for KYNA in the brain may provide insights into the pathophysiology of schizophrenia and Alzheimer's disease, disorders in which brain KYNA levels are increased and α7*nAChR functions are impaired.
Noradrenergic Inhibition of Midbrain Dopamine Neurons
Authors: Paladini Carlos A. , Williams John T.
Published: May 2004

Receptors that couple to phosphoinositide hydrolysis, which include metabotropic glutamate receptors (mGluRs) and muscarinic receptors, are known to either activate or inhibit the activity of dopamine cells depending on the pattern of receptor activation. Transient activation of α1adrenoceptors with norepinephrine (NE) resulted in an outward current in midbrain dopamine neurons recorded in brain slices. The NE-mediated outward current was induced by activation of a potassium conductance through release of calcium from intracellular stores. Unlike the mGluR-mediated outward current, the outward current induced by α1adrenoceptors often consisted of multiple peaks. Activation of α1adrenoceptors also induced a wave of calcium release that spread through the soma and proximal dendrites without a decline in amplitude or rate of propagation and therefore differed qualitatively from that induced by mGluRs. Finally, the α1adrenoceptor-activated outward current was more sensitive to the calcium store-depleting agents ryanodine and caffeine. Thus, although bothα1adrenoceptors and mGluRs mobilize calcium from intracellular stores, the mechanisms and pools of calcium differ. The results suggest that noradrenergic innervation of dopamine cells can directly inhibit the activity of dopamine cells. Psychostimulants, such as amphetamine, will therefore have a direct effect on the firing pattern of dopamine neurons through a combination of actions on dopamine and α1adrenoceptor activation.
The p75 Neurotrophin Receptor Can Induce Autophagy and Death of Cerebellar Purkinje Neurons
Authors: Florez-McClure Maria L. , Linseman Daniel A. , Chu Charleen T. , Barker Phil A. , Bouchard Ron J. , Le Shoshona S. , Laessig Tracey A. , Heidenreich Kim A.
Published: May 2004

The cellular mechanisms underlying Purkinje neuron death in various neurodegenerative disorders of the cerebellum are poorly understood. Here we investigate anin vitromodel of cerebellar neuronal death. We report that cerebellar Purkinje neurons, deprived of trophic factors, die by a form of programmed cell death distinct from the apoptotic death of neighboring granule neurons. Purkinje neuron death was characterized by excessive autophagic-lysosomal vacuolation. Autophagy and death of Purkinje neurons were inhibited by nerve growth factor (NGF) and were activated by NGF-neutralizing antibodies. Although treatment with antisense oligonucleotides to the p75 neurotrophin receptor (p75ntr) decreased basal survival of cultured cerebellar neurons, p75ntr-antisense decreased autophagy and completely inhibited death of Purkinje neurons induced by trophic factor withdrawal. Moreover, adenoviral expression of a p75ntr mutant lacking the ligand-binding domain induced vacuolation and death of Purkinje neurons. These results suggest that p75ntr is required for Purkinje neuron survival in the presence of trophic support; however, during trophic factor withdrawal, p75ntr contributes to Purkinje neuron autophagy and death. The autophagic morphology resembles that found in neurodegenerative disorders, suggesting a potential role for this pathway in neurological disease.
Echtzeit-Identifikation nichtlinearer instationärer Systeme mit RBF-Netzwerken (Real-time Identification of Non-linear Non-stationary Systems by RBF-Networks)
Authors: Rudenko Oleg G. , Bessonov Alexandr A. , Otto Peter , Wernstedt Jürgen
Published: May 2004

Der Beitrag behandelt den Einsatz Künstlicher Neuronaler Netze (KNN) zur Modellbildung für nichtlineare dynamische, stationäre und instationäre Systeme. Es wird gezeigt, dass Radiale Basisfunktionsnetze (RBF) in Zusammenhang mit dem neu entwickelten schnellen Mehrschritt-Algorithmus die besten Identifikationsergebnisse liefern. Die Struktur des Netzes wird während des Lernprozesses automatisch so lange erweitert, bis für alle Trainingsdaten eine definierte Fehlerschranke unterschritten wird. Am Beispiel einer nichtlinearen Differenzengleichung erster Ordnung mit einem zeitvarianten Faktor werden die Eigenschaften des neuen Identifikationsverfahrens demonstriert und mit anderen bekannten Verfahren verglichen.
LoPS – Lokales Positionsbestimmungssystem (LoPS – Local Positioning System)
Authors: Rudolph Alexander , Kleinschmidt Torsten , Blank Marcel , Adamy Jürgen
Published: May 2004

Zur Durchführung von Serviceaufgaben ist die Navigation eine Basiskompetenz eines mobilen Systems. In dieser Arbeit wird ein trilaterationsbasiertes Navigationssystem auf Ultraschallbasis vorgestellt. Das Lokale Positionsbestimmungs-System LoPS ermöglicht die Bestimmung von Objektpositionen in großen Räumen. LoPS zeichnet sich durch einfache Handhabung und flexible Einsatzmöglichkeiten aus. Bei der Entwicklung wurde großer Wert auf preisgünstige, robuste und unkomplizierte Sensorik gelegt. LoPS wurde als Referenzmesssystem für Roboternavigationsverfahren konzipiert, sein Einsatz ist aber in allen, auf die Bestimmung von kartesischen Koordinaten abzielenden Messaufgaben möglich.
What Is Ulcerative Colitis?
Authors: Voelker Rebecca
Published: February 2024

This JAMA Patient Page describes the condition of ulcerative colitis and its symptoms, diagnosis, and treatment options.
Compliance With US Federal Regulations on Waterpipe Tobacco Warnings on Packaging
Authors: Cornacchione Ross Jennifer , Zizzi Alexandra R. , Suerken Cynthia K. , Kimes Caroline , Soule Eric , Sutfin Erin L.
Published: February 2024

This cohort study reports the rate and degree of compliance with the Food and Drug Administration–mandated warning labels among waterpipe tobacco brands and products.
CADCA annual leadership meeting: Focus on youth
Authors: Knopf Alison
Published: February 2024

As always, youth are the focus of the annual meeting of CADCA, held last week in National Harbor, Maryland. In past years ADAW has been able to interview young people at the meeting and witness the success they have achieved throughout the year (see “Why primary prevention is important, and how to promote resilience: CADCA,” ADAW Feb. 10, 2020; https://onlinelibrary.wiley.com/ doi/10.1002/adaw.32617).
Single‐Transistor Optoelectronic Spiking Neuron with Optogenetics‐Inspired Spatiotemporal Dynamics
Authors: Li Hanxi , Hu Jiayang , Zhang Yishu , Chen Anzhe , Zhou Jiachao , Zhao Yuda , Xu Yang , Yu Bin
Published: February 2024

The visual system is crucial for human perception and learning, and the retina is responsible for pre‐processing visual information. Mimicking the neurobiological functions of the retina provides the basis for neuromorphic vision hardware. Here, an optogenetics‐inspired prototype capable of modifying neuron‐spiking behavior in a retina‐like manner is demonstrated. In addition to basic information processing, neuronal signal transmission in the retina is bio‐faithfully emulated using optical modulation, that is, neuronal firing is inhibited in the dark and activated upon illumination. The proposed single threshold‐switch field‐effect transistor optoelectronic neuron features an ultra‐compact design by integrating a gate‐modulated 2D MoS2 channel with a volatile threshold switch, and optoelectronic performance is achieved through a multi‐physics resistance‐matching mechanism. This study provides a promising pathway toward highly scalable and hierarchically designed spiking electronics, expanding the spectrum of neuromorphic hardware applications in the emerging field of biomimetic vision.
Chlorella‐Loaded Antibacterial Microneedles for Microacupuncture Oxygen Therapy of Diabetic Bacterial Infected Wounds
Authors: Gao Shuna , Rao Yu , Wang Xiaowei , Zhang Qiuyang , Zhang Zijun , Wang Yuxuan , Guo Jiangna , Yan Feng
Published: February 2024

Hypoxia and infection are urgent clinical problems in chronic diabetic wounds. Herein, living Chlorella‐loaded poly(ionic liquid)‐based microneedles (PILMN‐Chl) are constructed for microacupuncture oxygen and antibacterial therapy against methicillin‐resistant Staphylococcus aureus (MRSA)‐infected chronic diabetic wounds. The PILMN‐Chl can stably and continuously produce oxygen for more than 30 h due to the photosynthesis of the loaded self‐supported Chlorella. By combining the barrier penetration capabilities of microneedles, the continuous and sufficient oxygen supply of Chlorella, and the sterilization activities of PIL, the PILMN‐Chl can accelerate chronic diabetic wounds in vivo by topical targeted sterilization and hypoxia relief in deep parts of wounds. Thus, the self‐oxygen produced microneedles modality may provide a promising and facile therapeutic strategy for treating chronic, hypoxic, and infected diabetic wounds.
Bioengineered Ionic Liquid for Catheter‐Directed Tissue Ablation, Drug Delivery, and Embolization
Authors: Keum Hyeongseop , Albadawi Hassan , Zhang Zefu , Graf Erin , Santos Pedro Reck Dos , Gunduz Seyda , Oklu Rahmi
Published: February 2024

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter‐directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non‐survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans‐arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient‐derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo‐ and immunotherapy response in solid tumors.
Extracellular Matrix Scaffold‐Assisted Tumor Vaccines Induce Tumor Regression and Long‐Term Immune Memory
Authors: Pal Sanjay , Chaudhari Rohan , Baurceanu Iris , Hill Brenna J. , Nagy Bethany A. , Wolf Matthew T.
Published: February 2024

Injectable scaffold delivery is a strategy to enhance the efficacy of cancer vaccine immunotherapy. The choice of scaffold biomaterial is crucial, impacting both vaccine release kinetics and immune stimulation via the host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues facilitate a pro‐healing inflammatory response that promotes local cancer immune surveillance. Here, an ECM scaffold‐assisted therapeutic cancer vaccine that maintains an immune microenvironment consistent with tissue reconstruction is engineered. Several immune‐stimulating adjuvants are screened to develop a cancer vaccine formulated with decellularized small intestinal submucosa (SIS) ECM scaffold co‐delivery. It is found that the STING pathway agonist cyclic di‐AMP most effectively induces cytotoxic immunity in an ECM scaffold vaccine, without compromising key interleukin 4 (IL‐4) mediated immune pathways associated with healing. ECM scaffold delivery enhances therapeutic vaccine efficacy, curing 50–75% of established E.G‐7OVA lymphoma tumors in mice, while none are cured with soluble vaccine. SIS‐ECM scaffold‐assisted vaccination prolonged antigen exposure is dependent on CD8+ cytotoxic T cells and generates long‐term antigen‐specific immune memory for at least 10 months post‐vaccination. This study shows that an ECM scaffold is a promising delivery vehicle to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro‐healing immune hallmarks.
Intergrating Hollow Multishelled Structure and High Entropy Engineering toward Enhanced Mechano‐Electrochemical Properties in Lithium Battery
Authors: Liu Xuefeng , Yu Yingjie , Li Kezhuo , Li Yage , Li Xiaohan , Yuan Zhen , Li Hang , Zhang Haijun , Gong Mingxing , Xia Weiwei , Deng Yaping , Lei Wen
Published: February 2024

Hollow multishelled structures (HoMSs) are attracting great interest in lithium‐ion batteries as the conversion anodes, owing to their superior buffering effect and mechanical stability. Given the synthetic challenges, especially elemental diffusion barrier in the multimetal combinations, this complex structure design has been realized in low‐ and medium‐entropy compounds so far. It means that poor reaction reversibility and low intrinsic conductivity remain largely unresolved. Here, a hollow multishelled (LiFeZnNiCoMn)3O4 high entropy oxide (HEO) is developed through integrating molecule and microstructure engineering. As expected, the HoMS design exhibits significant targeting functionality, yielding satisfactory structure and cycling stability. Meanwhile, the abundant oxygen defects and optimized electronic structure of HEO accelerate the lithiation kinetics, while the retention of the parent lattice matrix enables reversible lithium storage, which is validated by rigorous in situ tests and theoretical simulations. Benefiting from these combined properties, such hollow multishelled HEO anode can deliver a specific capacity of 967 mAh g−1 (89% capacity retention) after 500 cycles at 0.5 A g−1. The synergistic lattice and volume stability showcased in this work holds great promise in guiding the material innovations for the next‐generation energy storage devices.
Dopant Control of Solution‐Processed CuI:S for Highly Conductive p‐Type Transparent Electrode
Authors: Son Minki , Kim Ga Hye , Song Okin , Park ChanHu , Kwon Sunbum , Kang Joohoon , Ahn Kyunghan , Kim Myung‐Gil
Published: February 2024

Copper iodide (CuI) has garnered considerable attention as a promising alternative to p‐type transparent conducting oxides owing to its low cation vacancy formation energy, shallow acceptor level, and readily modifiable conductivity via doping. Although sulfur (S) doping through liquid iodination has exhibited high efficacy in enhancing the conductivity with record high figure of merit (FOM) of 630 00 MΩ−1, solution‐processed S‐doped CuI (CuI:S) for low‐cost large area fabrication has yet to be explored. Here, a highly conducting CuI:S thin‐film for p‐type transparent conducting electrode (TCE) is reported using low temperature solution‐processing with thiourea derivatives. The optimization of thiourea dopant is determined through a comprehensive acid‐base study, considering the effects of steric hindrance. The modification of active groups of thioureas facilitated a varying carrier concentration range of 9 × 1018–2.52 × 1020 cm−3 and conductivities of 4.4–390.7 S cm−1. Consequently, N‐ethylthiourea‐doped CuI:S exhibited a FOM value of 7 600 MΩ−1, which is the highest value among solution‐processed p‐type TCEs to date. Moreover, the formulation of CuI:S solution for highly conductive p‐type TCEs can be extended to CuI:S inks, facilitating high‐throughput solution‐processes such as inkjet printing and spray coating.
Pizza Oven Processing of Organohalide Perovskites (POPOP): A Simple, Versatile and Efficient Vapor Deposition Method
Authors: Guesnay Quentin , Sahli Florent , Artuk Kerem , Turkay Deniz , Kuba Austin G. , Mrkyvkova Nada , Vegso Karol , Siffalovic Peter , Schreiber Frank , Lai Huagui , Fu Fan , Ledinský Martin , Fürst Nicolas , Schafflützel Aymeric , Bucher Cédric , Jeangros Quentin , Ballif Christophe , Wolff Christian M.
Published: February 2024

Hybrid vapor deposition is one of the most appealing processes for perovskite photovoltaics fabrication, thanks to its versatile nature. By using sequentially different vapor deposition processes tailored to the inorganic and organic perovskite precursors' peculiarities, this type of process gives access to the full potential of vapor deposition. While vapor deposition of metal halides is well understood and mastered, vapor deposition of organohalide species is much more delicate (degradation of vapors, high vapor pressure, setup‐specific constraints). Here, a novel close space sublimation system is reported and in‐depth insights on the conversion into perovskite of a metal halide template are provided. In this evolution of the process, the substrate coated with metal halide template and the organohalide source are loaded together in a dedicated holder, then transferred into a vacuum chamber on a heating element already at temperature setpoint. The system enables a simple, fast, low‐cost, and easy‐to‐reproduce organohalide vapor deposition process. The formation of the perovskite in situ and identification different conversion regimes are studied. Furthermore, the influence of the chemical environment and chamber design on the process are discussed. Compositional tuning and additive engineering in the process are processed and fabricate proof of concept photovoltaic devices reaching high fill factors of 80% and 17% power conversion efficiency for a bandgap of 1.63 eV.
Multifunctional Cellulose Nanocrystals Electrolyte Additive Enable Ultrahigh‐Rate and Dendrite‐Free Zn Anodes for Rechargeable Aqueous Zinc Batteries
Authors: Wu Qing , Huang Jun , Zhang Jinlong , Yang Song , Li Yue , Luo Fusheng , You Yang , Li Yunqi , Xie Haibo , Chen Yiwang
Published: February 2024

The design of aqueous zinc (Zn) chemistry energy storage with high rate‐capability and long serving life is a great challenge due to its inhospitable coordination environment and dismal interfacial chemistry. To bridge this big gap, herein, we build a highly reversible aqueous Zn battery by taking advantages of the biomass‐derived cellulose nanocrystals (CNCs) electrolyte additive with unique physical and chemical characteristics simultaneously. The CNCs additive not only serves as fast ion carriers for enhancing Zn2+ transport kinetics but regulates the coordination environment and interface chemistry to form dynamic and self‐repairing protective interphase, resulting in building ultra‐stable Zn anodes under extreme conditions. As a result, the engineered electrolyte system achieves a superior average coulombic efficiency of 97.27 % under 140 mA cm−2, and steady charge–discharge for 982 h under 50 mA cm−2, 50 mAh cm−2, which proposes a universal pathway to challenge aqueous Zn chemistry in green, sustainable, and large‐scale applications.
Hierarchical self‐assembly of tannic acid/diethylenetriamine on polypropylene for high‐performance separator
Authors: Wang Haihua , Han Yun , Liu Xuan , Sun Liyu , Niu Huizhu , Du Yifan , Wang Jie
Published: February 2024

In lithium‐ion batteries (LIBs), separator is used to provide a barrier between the anode and cathode and provide freedom for the transport of lithium‐ions, which serves a key function in inhibiting internal short circuit and improving the battery safety. The limited wettability of commercial polyolefin separators in electrolytes restricts its utilization in extreme environmental conditions. In our work, we choose polypropylene (PP) as the precursor and can address the issue of poor wettability through suitable modification methods. Tannic acid (TA) and diethylenetriamine (DETA) were utilized to coat PP separator via hierarchical self‐assembly approach, and the coating is further stabilized by taking advantage of the specific oxidizing properties of sodium periodate. This method scarcely increases the separator thickness or sacrifices the microporous structure of the original separator. The improved separator not only exhibits outstanding wetting capability and relatively high ion conductivity (1.24 mS cm−1), but also has the highest lithium‐ion migration number of 0.74. This indicates that when the modified separator is applied to LIBs, its electrochemical performance is significantly enhanced. The enhancement in electrochemical performance of LIBs is attributed to the strong absorption and retention ability of the coating on the separator. The reversible capacity of Li/PP‐TD2 separator/LiFePO4 battery is 144.3 mAh g−1 at 2C, which is higher than that of PP separator (117.1 mAh g−1) under the same current density. Even after 200 cycles, the PP‐TD2 separator with two‐layer assembly modification still maintains a higher coulombic efficiency of 97.55% and a discharge capacity of 96.6%. This hierarchical self‐assembly modification of PP provides an effective approach for fabricating high‐performance separator.
Green horizons: Unleashing green innovation through green business strategies and competencies
Authors: Ashraf Sheikh Farhan , Li Cai , Wattoo Muhammad Umair , Murad Majid , Mahmood Babak
Published: February 2024

China's manufacturing industry environmental regulations portray a strategic change towards sustainable development. The study examines how green business strategies and competencies enhance green innovation for manufacturing firm performance. The study approach included surveying senior managers from Chinese manufacturing firms. The hypotheses were tested running partial least squares structural equation modeling using 459 firms. The results reveal the complex relationships between these factors, showing how value co‐creation and absorptive ability generate innovation and business performance through green strategies and capabilities. Furthermore, green value co‐creation enhances a firm's green innovation and helps to achieve firm performance. This study contributes to the corpus of knowledge on sustainable manufacturing techniques and helps firms succeed in an environmentally conscious society.
So … are family firms more sustainable? On the economic, social and environmental sustainability of family SMEs
Authors: Herrero Inés , López Cristina , Ruiz‐Benítez Rocío
Published: February 2024

In this work, we address the conflicting results that appear in the literature regarding whether family firms are more or less sustainable than nonfamily firms in each of the three dimensions, by focusing on the group that has been largely disregarded: small‐ and medium‐sized family firms (family SMEs). We set a number of hypotheses, which we test in a sample of Spanish manufacturing firms in the food and beverages sector, using structural equation modelling. We conclude that competing arguments coexist both in favour and against these firms being more or less environmentally and economically sustainable, which finally balance themselves out. However, we found out that family firms tend to take greater care of their closer stakeholders, which, together with the importance given to their social relations with external stakeholders, make them champions in terms of social sustainability. Our results show that family firms are able to be more socially sustainable without having to compromise their economic performance in the long term. Finally, as family firms are not an homogeneous group, we analyse whether our results are firm specific, taking into account the role that the number of generations that the family has run the business and the number of generations currently involved in the business exert on firm sustainability, thereby reaching at very interesting conclusions.
Synthesis of Novel Acetyl‐11‐keto‐β‐boswellic Acid Derivatives as Potential Anti‐GBM Agents
Authors: Sun Mingxia , Zhang Sen , Wang Jinhua , Du Guanhua , Ji Tengfei
Published: February 2024

Acetyl‐11‐keto‐β‐boswellic acid (AKBA) is known to inhibit the growth of glioblastoma (GBM) cells and subcutaneous GBM. A series of acetyl‐11‐keto‐β‐boswellic acid (AKBA) derivatives containing the oxime‐ester functionality or amide side chains were synthesized, and their anti‐GBM activities were evaluated. Some of these compounds exhibited significant inhibitory activity against cell proliferation in U87 and U251 GBM cell lines, with IC50 values in the micromolar concentration range. Cellular thermal shift analysis showed that A‐01 and A‐10 improved the thermal stability of FOXM1, indicating that these highly active compounds may directly bind to FOXM1 in cells. Docking studies of the two most active compounds, A‐01 and A‐10, revealed key interactions between these compounds and the active site of FOXM1, in which the amide moiety at the C‐24 position was essential for improving the activity. These results suggested that A‐10 is a suitable lead molecule for the development of FOXM1 inhibitors. Thus, the rational design of AKBA derivatives with amide side chains holds significant potential for discovering of a new class of triterpenoids capable of inhibiting GBM cell proliferation.
A case of MYH7 and MYH9 genes variants with cardiomyopathy and macrothrombocytopenia
Authors: Ikawa Yasuhiro , Nakamura Taichi , Fujino Noboru , Uchiyama Toru , Ishiguro Akira , Takenaka Mika , Sakai Yuta , Noguchi Kazuhiro , Fujiki Toshihiro , Wada Taizo
Published: February 2024

Key Clinical Message.

A 15‐year‐old girl developed inherited cardiomyopathy and macrothrombocytopenia revealing pathogenic variants of both MYH7 and MYH9 genes. This underlies the importance of repeated genetic testing in diagnosing and managing inherited disorders.

The MYH7 and MYH9 genes encode for distinct myosin heavy chain proteins. Our case features a 15‐year‐old girl, presenting with inherited cardiomyopathy and macrothrombocytopenia, revealing distinct pathogenic variants of both MYH7 and MYH9 genes. This underlines the relevance of genetic testing and personalized medicine in diagnosing and managing inherited disorders.
Oxidative Decarbonylation of an Azacalixpyridine‐Supported Mo(0)‐Tricarbonyl to a Mo(VI)‐Trioxo Complex with Dioxygen in Solution and on Au(111): Determination of Molecular Mechanism
Authors: Clausen Kai Uwe , Pienack Nicole , Gripp Joachim , Tuczek Felix
Published: February 2024

The conversion of an azacalixpyridine‐supported Mo(0) tricarbonyl into a Mo(VI) trioxo complex with dioxygen (O2) is investigated in homogeneous solution and in a molecular film adsorbed on Au(111) using a variety of spectroscopic and analytical methods. These studies in particular show that the dome‐shaped carbonyl complex adsorbed on the metal surface has the ability to bind and activate gaseous oxygen, overcoming the so‐called surface trans‐effect. Furthermore, the rate of the conversion dramatically increases by irradiation with light. This observation is explained with the help of complementary DFT calculations and attributed to two different pathways, a thermal and a photochemical one. Based on the experimental and theoretical findings, a molecular mechanism for the conversion of the carbonyl to the oxo complex is derived.
Pinpointing Acidic Residues in Proteins
Authors: Xuan Weimin , Ma Jun‐An
Published: February 2024

It is of great importance to pinpoint specific residues or sites of a protein in biological contexts to enable desired mechanism of action for small molecules or to precisely control protein function. In this regard, acidic residues including aspartic acid (Asp) and glutamic acid (Glu) hold great potential due to their great prevalence and unique function. To unlock the largely untapped potential, great efforts have been made recently by synthetic chemists, chemical biologists and pharmacologists. Herein, we would like to highlight the remarkable progress and particularly introduce the electrophiles that exhibit reactivity to carboxylic acids, the light‐induced reactivities to carboxylic acids and the genetically encoded noncanonical amino acids that allow protein manipulations at acidic residues. We also comment on certain unresolved challenges, hoping to draw more attention to this rapidly developing area.
Chemovoltaic effect for renewable liquid and vapor fuels on semiconductor surfaces
Authors: Alizadeh Mahdi , Radevici Ivan , Li Shengyang , Oksanen Jani
Published: February 2024

The chemovoltaic effect – generation of electronic excitation by exergonic redox reactions – has been observed on metallic surfaces of Schottky junctions and is proving to be pivotal in explaining in detail the momentum conservation relations of chemically active collisions. As shown in this work, it can hold keys for direct chemical energy harvesting by semiconductor solar cells. To study the possibilities of chemovoltaic energy conversion by semiconductors, we have modeled and designed an ‘electrolyte‐free fuel cell’ formed by a GaAs diode that can host electrochemical fuel oxidation and oxidant reduction reactions on its conduction and valence bands and as a result convert renewable chemical energy (as well as light) into electricity. The experimental results show that exposing the surface of a suitably designed solar cell to methanol liquid or vapor in the presence of oxygen or hydrogen peroxide leads to the generation of electrical power.