bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification
Authors: Gagliardi Filippo , De Domenico Pierfrancesco , Garbin Enrico , Snider Silvia , Mortini Pietro
Published: September 2023

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single‐patient‐level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single‐patient‐level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low‐grade glioma (6%), high‐grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36‐month follow‐up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high‐grade gliomas (8mo). The 3‐year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low‐grade pineal lesions, 66% for high‐grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3‐year progression‐free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low‐grade pineal, 66% for high‐grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.
Fibroblast growth factor 9 (FGF9)‐mediated neurodegeneration: Implications for progressive multiple sclerosis?
Authors: Thümmler Katja , Wrzos Claudia , Franz Jonas , McElroy Daniel , Cole John J. , Hayden Lorna , Arseni Diana , Schwarz Friedrich , Junker Andreas , Edgar Julia M. , Kügler Sebastian , Neef Andreas , Wolf Fred , Stadelmann Christine , Linington Christopher
Published: September 2023

Aims

Fibroblast growth factor (FGF) signalling is dysregulated in multiple sclerosis (MS) and other neurological and psychiatric conditions, but there is little or no consensus as to how individual FGF family members contribute to disease pathogenesis. Lesion development in MS is associated with increased expression of FGF1, FGF2 and FGF9, all of which modulate remyelination in a variety of experimental settings. However, FGF9 is also selectively upregulated in major depressive disorder (MDD), prompting us to speculate it may also have a direct effect on neuronal function and survival.

Methods

Transcriptional profiling of myelinating cultures treated with FGF1, FGF2 or FGF9 was performed, and the effects of FGF9 on cortical neurons investigated using a combination of transcriptional, electrophysiological and immunofluorescence microscopic techniques. The in vivo effects of FGF9 were explored by stereotactic injection of adeno‐associated viral (AAV) vectors encoding either FGF9 or EGFP into the rat motor cortex.

Results

Transcriptional profiling of myelinating cultures after FGF9 treatment revealed a distinct neuronal response with a pronounced downregulation of gene networks associated with axonal transport and synaptic function. In cortical neuronal cultures, FGF9 also rapidly downregulated expression of genes associated with synaptic function. This was associated with a complete block in the development of photo‐inducible spiking activity, as demonstrated using multi‐electrode recordings of channel rhodopsin‐transfected rat cortical neurons in vitro and, ultimately, neuronal cell death. Overexpression of FGF9 in vivo resulted in rapid loss of neurons and subsequent development of chronic grey matter lesions with neuroaxonal reduction and ensuing myelin loss.

Conclusions

These observations identify overexpression of FGF9 as a mechanism by which neuroaxonal pathology could develop independently of immune‐mediated demyelination in MS. We suggest targeting neuronal FGF9‐dependent pathways may provide a novel strategy to slow if not halt neuroaxonal atrophy and loss in MS, MDD and potentially other neurodegenerative diseases.
Coronary artery complications with left bundle branch area pacing: A review of literature
Authors: Raza Muhammad Hassan , Maqbool Muhammad Usama , Kumar Sunil , Malik Jahanzeb , Ali Sameer , Khan Zahoor Aslam
Published: September 2023

Left bundle branch area pacing (LBBAP) is an emerging technique in cardiac resynchronization therapy that shows promise in improving ventricular synchrony and clinical outcomes in patients with heart failure. However, the potential risk of coronary artery complications with LBBAP necessitates careful attention and management. This literature review explores the mechanisms, acute coronary events, and clinical implications associated with coronary artery complications in LBBAP. The mechanism of coronary injury with LBBAP involves mechanical trauma, altered coronary blood flow dynamics, and endothelial damage. Acute coronary events such as myocardial ischemia, acute coronary syndromes, and coronary artery dissection can occur during or after LBBAP, leading to significant clinical implications including the need for prompt intervention and potential impact on long‐term outcomes. To avoid coronary injury and acute coronary syndrome with LBBAP, specific care strategies are recommended. These include thorough pre‐procedural evaluation, expert operator technique, optimization of hemodynamics and ventricular synchrony, close monitoring for ischemic events, collaboration with cardiology specialists, and long‐term follow‐up. The clinical implications of coronary artery complications with LBBAP necessitate careful patient selection, informed decision‐making, and a multidisciplinary approach. Future directions in this field include advancements in procedural techniques, technological innovations, risk stratification strategies, enhanced imaging modalities, research on mechanisms and prevention, and collaboration among stakeholders. By implementing these strategies and focusing on future advancements, healthcare providers can minimize the risk of coronary artery complications with LBBAP and optimize patient outcomes in cardiac resynchronization therapy.
Effects of far‐red light on the behaviour and reproduction of the zoophytophagous predator Macrolophus pygmaeus and its interaction with a whitefly herbivore
Authors: Meijer Davy , Hopkoper Syb , Weldegergis Berhane T. , Westende Wendy van't , Gort Gerrit , van Loon Joop J. A. , Dicke Marcel
Published: September 2023

Plants can detect neighbouring plants through a reduction in the ratio between red and far‐red light (R:FR). This provides a signal of plant–plant competition and induces rapid plant growth while inhibiting defence against biotic stress, two interlinked responses designated as the shade avoidance syndrome (SAS). Consequently, the SAS can influence plant–herbivore interactions that could cascade to higher trophic levels. However, little is known about how the expression of the SAS can influence tritrophic interactions. We investigated whether changes in R:FR affect the emission of herbivore‐induced plant volatiles (HIPVs), and whether these changes influence the attraction of the zoophytophagous predator Macrolophus pygmaeus. We also studied how the expression of the SAS and subsequent inhibition of plant defences affects the reproduction of M. pygmaeus in both the presence and absence of the greenhouse whitefly (WF) (Trialeurodes vaporariorum) as arthropod prey. The results show that changes in R:FR have little effect on HIPV emissions and predator attraction. However, a reduction in R:FR leads to increased reproduction of both the predator and the WFs. We discuss that shade avoidance responses can increase the population development of M. pygmaeus through a combination of reduced plant defences and increased herbivore densities.
Neuropathological substrate of incident dementia in older patients with schizophrenia: A clinicopathological study
Authors: Arafuka Shusei , Fujishiro Hiroshige , Torii Youta , Sekiguchi Hirotaka , Habuchi Chikako , Miwa Ayako , Yoshida Mari , Iritani Shuji , Iwasaki Yasushi , Ikeda Masashi , Ozaki Norio
Published: September 2023

Aim

Clinical studies reported that patients with schizophrenia are at a higher risk of developing dementia than people without schizophrenia. However, early neuropathological studies have shown that the incidence of Alzheimer's disease (AD) in schizophrenia patients does not differ from that in controls. These inconsistent results may be attributable to the inclusion of non‐AD dementia, but there have been few clinicopathological studies in older patients with schizophrenia based on the current neuropathological classification. This study aimed to investigate the neuropathological basis of incident dementia in older patients with schizophrenia.

Methods

We systematically examined 32 brains of old patients with schizophrenia using standardized pathological methods. The severity of dementia‐related neuropathologies was analyzed using standardized semiquantitative assessments. After excluding patients who fulfilled the neuropathological criteria, clinicopathological variables were compared between patients with and without incident dementia to identify potential differences.

Results

Seven patients fulfilled the pathological criteria for AD (n = 3), argyrophilic grain disease (AGD) (n = 2), dementia with Lewy bodies (n = 1), and AGD/progressive supranuclear palsy (n = 1). Among 25 patients for whom a neuropathological diagnosis was not obtained, 10 had dementia, but the clinicopathological findings did not differ from the remaining 15 patients without dementia.

Conclusion

Two types of older schizophrenia patient present dementia: patients with co‐existing neurodegenerative disease and patients who do not meet pathological criteria based on the current classification. To understand the neurobiological aspects of incident dementia in older patients with schizophrenia, further clinicopathological studies are needed that do not simply analyze incident dementia as a comorbidity of conventional dementia‐related neuropathologies.
The role of frailty among the predictors of depression on informal caregivers of older adults: a mediation analysis
Authors: Vrettos Ioannis , Voukelatou Panagiota , Kyvetos Andreas , Makrilakis Konstantinos , Sfikakis Petros P. , Raptis Athanasios , Niakas Dimitris
Published: September 2023

Background

Providing care for older adults has been associated with the presence of depressive symptoms among their informal caregivers. Numerous caregivers and older adults' characteristics have been mentioned as predictors of caregivers' depression. However, studies dealing with the impact of older adults' frailty status on caregivers' depression are scarce. This study was conducted to clarify the precise relationship between caregivers' depression, caregivers' burden, caregivers' characteristics and patients' characteristics, including frailty, among the variables that may have an impact on caregivers' depression.

Methods

In this cross‐sectional study, patients and caregivers' characteristics were recorded for 311 patient‐caregiver dyads, when the patient was admitted to the hospital. For the purpose of the study, a mediation analysis was used with patients and caregiver characteristics considered to be predictors, subjective caregivers' burden as the mediator, and caregivers’ depression as the outcome variable.

Results

Only patients' frailty and caregivers' subjective burden had a direct effect on caregivers' depression. Moreover, caregivers' gender, patients' frailty status and comorbidity, duration of caregiving, and the relationship with the patient, had an indirect effect through caregivers' burden that acted as mediator. Regarding total effects, caregivers burden followed by patients' frailty status had the greater impact on caregivers' depression.

Conclusions

By organising interventions to reduce caregivers' depression, patients' frailty status could be among the targets of those interventions considering that frailty might be delayed or reversed.
Fostering digital literacy among small and micro‐enterprises: digital transformation as an open and guided innovation process
Authors: Coco Nunzia , Colapinto Cinzia , Finotto Vladi
Published: September 2023

This study examines how micro, small and medium‐sized enterprises (MSMEs) can overcome resistance to digitalization through open innovation and design thinking techniques. By analyzing data from 74 Italian MSMEs participating in an Industry 4.0 adoption policy initiative, the research explores strategies to increase the adoption of new technologies. Using an action‐research analytical approach of 9 months, we identify factors facilitating the digitization process in MSMEs and achieving digitization policy objectives. This paper emphasizes the role of training, networking, and co‐creation initiatives in enhancing MSMEs' digital literacy and promoting the adoption of new technologies. These findings contribute to the ongoing debate on MSMEs' digital transformation and inform policy‐making by highlighting both enablers and barriers. Ultimately, the research aims to provide valuable insights for practitioners and policymakers seeking to support MSMEs in their digitalization journey.
Fisheries local action group managers as reflexive practitioners: The enhancement of projects and networks and the renewal of the Finnish fishing livelihood
Authors: Salmi Pekka , Svels Kristina
Published: September 2023

The implementation of the European Fisheries Local Action Group (FLAG) system applies a neo‐endogenous approach, which can restructure public intervention in favour of a mosaic of local territories. By resting on a Finnish case study, this article studies the local adaptation of the FLAG system and how FLAG managers are positioned as intermediaries in horizontal and vertical networks that enhance local fisheries’ livelihoods. The analysis of the FLAG system's approaches and various roles of the managers is based on qualitative interviews and a stakeholder survey, set in the interactive governance framework. Our findings show how via its intermediary role, expertise, commitment and networking, the FLAG system, and especially FLAG managers, can mend the failures of the governance system. We conclude that the recruitment of the right type of FLAG managers can be a path towards the enhancement of local small‐scale fishers in a well‐functioning governance system
.
Regional Investment Flows from Greece to Bulgaria in the COVID‐19 context: is there a halt trend?
Authors: Kapitsinis N. , Rasvanis E. , Topaloglou L. , Manetos P. , Kallioras D.
Published: September 2023

This paper offers a comprehensive analysis of the investment flows from Greek to Bulgarian regions against the context of COVID‐19. Employing a mixed research method, it investigates the initial impact of COVID‐19 on regional FDI flows from Greece to Bulgaria and intends to explore to which extent the pandemic acts as an impediment to firm relocation, by examining regional investment flows from 2013 to 2020. The effects of the COVID‐19 macroeconomic shock are placed in the context of the existing conditions shaped by the 2008 global economic crisis. The paper also attempts to provide a critical insight of factors underlying investment flows. The results indicate that there was a limited investment halt but no disinvestment from the Greek to Bulgarian regions in the first year of the COVID‐19 outbreak. Low and stable taxation, cheap labour and efficient regulatory regime attract Greek investments in Bulgaria.
By Design: How People Adapt to Cognitive Limitations in Politics
Authors: Lupia Arthur
Published: September 2023

Elections, jury deliberations, lawmaking, high‐stakes negotiations and related activities are human attempts to answer the question “How should we live?” Collectively, we know these activities as politics. Politics are how societies attempt to reconcile diverse individual needs with potential benefits of social coordination. People's beliefs about what others will do ainfluence many political strategies and outcomes. This article reviews how properties of cognition affect these political phenomena. Contrary to the common belief that many citizens are too ignorant to make competent political decisions, we focus on a central finding of social science—how societies can design contexts and environments to overcome individual cognitive limitations. These adaptations expand societal capacities to provide essential goods, services, and protections. In addition to explaining these adaptations, we also show how greater collaborations between cognitive science and the social sciences can help societies do even better.
Evolutionary analysis of conserved non‐coding elements subsequent to whole‐genome duplication in opium poppy
Authors: Xu Yu , Bush Stephen J. , Yang Xinyi , Xu Linfeng , Wang Bo , Ye Kai
Published: September 2023

Whole‐genome duplication (WGD) leads to the duplication of both coding and non‐coding sequences within an organism's genome, providing an abundant supply of genetic material that can drive evolution, ultimately contributing to plant adaptation and speciation. Although non‐coding sequences contain numerous regulatory elements, they have been understudied compared to coding sequences. In order to address this gap, we explored the evolutionary patterns of regulatory sequences, coding sequences and transcriptomes using conserved non‐coding elements (CNEs) as regulatory element proxies following the recent WGD event in opium poppy (Papaver somniferum). Our results showed similar evolutionary patterns in subgenomes of regulatory and coding sequences. Specifically, the biased or unbiased retention of coding sequences reflected the same pattern as retention levels in regulatory sequences. Further, the divergence of gene expression patterns mediated by regulatory element variations occurred at a more rapid pace than that of gene coding sequences. However, gene losses were purportedly dependent on relaxed selection pressure in coding sequences. Specifically, the rapid evolution of tissue‐specific benzylisoquinoline alkaloid production in P. somniferum was associated with regulatory element changes. The origin of a novel stem‐specific ACR, which utilized ancestral cis‐elements as templates, is likely to be linked to the evolutionary trajectory behind the transition of the PSMT1‐CYP719A21 cluster from high levels of expression solely in P. rhoeas root tissue to its elevated expression in P. somniferum stem tissue. Our findings demonstrate that rapid regulatory element evolution can contribute to the emergence of new phenotypes and provide valuable insights into the high evolvability of regulatory elements.
WILL WE KNOW THEM WHEN WE MEET THEM? HUMAN CYBORG AND NONHUMAN PERSONHOOD
Authors: Turner Léon
Published: September 2023

In this article, I assess (1) whether some cyborgs and AI robots can theoretically be considered persons; and (2) how we will know if/when they have attained personhood. Since our discourses of personhood are inherently pluralistic and our concepts of both humanness and personhood are inherently nebulous, both some cyborgs, and some AI robots, I conclude, could theoretically be considered persons depending on what, exactly, one means by “person.” The practical problem of how we distinguish them from nonpersonal AI entities is, however, both more important, and much more difficult to solve. In conversation with various secular and theological accounts of relational personhood, I argue that only by treating AI entities as persons by default might we avoid the potentially catastrophic consequences of mistakenly denying personhood to an entire group of eligible entities.
‘Evolutionary poker’: an agent‐based model of interactome emergence and epistasis tested against Lenski's long‐term E. coli experiments
Authors: Root‐Bernstein Robert S. , Bernstein Morton I.
Published: September 2023

A simple agent‐based model is presented that produces results matching the experimental data found by Lenski's group for ≤50,000 generations of Escherichia coli bacteria under continuous selective pressure. Although various mathematical models have been devised previously to model the Lenski data, the present model has advantages in terms of overall simplicity and conceptual accessibility. The model also clearly illustrates a number of features of the evolutionary process that are otherwise not obvious, such as the roles of epistasis and historical contingency in adaptation and why evolution is time irreversible (‘Dollo's law’). The reason for this irreversibility is that genomes become increasingly integrated or organized, and this organization becomes a novel selective factor itself, against which future generations must compete. Selection for integrated or synergistic networks, systems or sets of mutations or traits, not for individual mutations, confers the main adaptive advantage. The result is a punctuated form of evolution that follows a logarithmic occurrence probability, in which evolution proceeds very quickly when interactomes begin to form but which slows as interactomes become more robust and the difficulty of integrating new mutations increases. Sufficient parameters exist in the game to suggest not only how equilibrium or stasis is reached but also the conditions in which it will be punctuated, the factors governing the rate at which genomic organization occurs and novel traits appear, and how population size, genome size and gene variability affect these.

image
Exploring the Impact of CO2 Atmosphere on Propane Moderate or Intense Low-Oxygen Dilution Combustion: A Numerical Simulation Study
Authors: Pengsheng Shi , Tianyou Zhang , Weijuan Yang , Zhijun Zhou , Junhu Zhou , Jianzhong Liu
Published: September 2023

Moderate or intense low-oxygen dilution (MILD) combustion is a promising combustion technology widely recognized by the international combustion community. In this study, numerical simulation was used to investigate the effects of CO2 atmosphere on MILD combustion of propane in a 20-KW furnace.The results show that the O2/CO2 atmosphere leads to a lower average temperature in the furnace, better temperature uniformity, and more uniform distribution of OH and CH2O compared to MILD combustion in the N2/O2 atmosphere. Propane MILD combustion is established well under the physical and chemical effects of CO2. An analytical approach is proposed to describe the physical and chemical effects of CO2 on MILD combustion. The physical effect of CO2 shortens the ignition delay time and advances the pyrolysis and ignition of propane, which causes a high-temperature zone in the front furnace and reduces the temperature uniformity in MILD combustion. However, the chemical effect of CO2 dominates the establishment of the MILD combustion by increasing the ignition delay time and reducing burning rates, with the help of the physical effects of CO2 by intensifying the entrainment in the furnace. Thus, the overall effects of CO2 lead to enhanced temperature uniformity by enlarging the area and evening the temperature of both the ignition zone and combustion zone. These findings provide valuable insights into the physical and chemical mechanisms of CO2 in MILD combustion and have important implications for optimizing combustion processes for improved efficiency and reduced emissions.
Thermohydrodynamic Analysis of a Controllable Stiffness Foil Bearing With Shape Memory Alloy Springs: Experimental Tests and Theoretical Predictions
Authors: Cao Yuanlong , Hao Kaiyuan , Fan Jiahui , Zhang Hang , Guan Hanqing , Feng Kai
Published: September 2023

Shape memory alloy (SMA)-gas foil bearings (SMA-GFBs) are novel gas bearings comprising top foil, SMA springs, and housing. The radial clearance, stiffness, and damping coefficients of SMA-GFBs can be regulated by the bearing temperature which is determined by the electric heating of SMA springs and the cooling flow. A 3D thermohydrodynamic model (THD) considering the conduction and convection of the top foil, bearing housing, and hollow rotor, and the heat energy of heated SMA springs is presented to simulate the temperature distribution of SMA-GFBs at different rotational speeds, heating powers, and cooling flows. Centrifugal growth of the rotor and thermal expansions of the rotor, SMA springs, and bearing housing are also considered. A test rig is built to measure the bearing temperature and to validate the effectiveness of the theoretical model and circumferential cooling mode. Parametric studies are conducted with different speeds, heating powers, and cooling flows. The heat transfer ratios of the rotor and substructure are also compared. Compared to the temperature differences of the bearing temperature in the circumferential or axial directions, the effects of rotational speed and cooling flow on the bearing temperature are more apparent. The phase transition process of SMA spring can be controlled by adjusting the rotor speed and the cooling flow reasonably, and then the temperature characteristics of SMA-GFB can be changed. The temperature depending on the compressed gas film and heated SMA springs and cooling flow can be adjusted to confirm the feasibility of actively altering the performance of the bearing-rotor system.
The Impact of Multisession Sleep-Hygiene Strategies on Sleep Parameters in Elite Swimmers
Authors: Pasquier Florane , Pla Robin , Bosquet Laurent , Sauvet Fabien , Nedelec Mathieu , _ _
Published: September 2023

Purpose: Short sleep duration and poor sleep quality are common in swimmers. Sleep-hygiene strategies demonstrated beneficial effects on several sleep parameters. The present study assessed the impact of a multisession sleep-hygiene training course on sleep in elite swimmers. Methods: Twenty-eight elite swimmers (17 [2] y) participated. The sleep-hygiene strategy consisted of 3 interventions. Sleep was measured by actigraphy for 7 days before the beginning of the intervention (baseline), after the first collective intervention (postintervention), after the second collective intervention (postintervention 2), and, finally, after the individual intervention (postintervention 3). The Epworth Sleepiness Scale (ESS) was completed concurrently. Swimmers were classified into 2 groups: nonsomnolent (baseline ESS score ≤ 10, n = 13) and somnolent (baseline ESS score ≥ 11, n = 15). Results: All swimmers had a total sleep time of <8 hours per night. Sixty percent of swimmers were moderately morning type. Later bedtime, less time in bed, and total sleep time were observed in the somnolent group compared with the nonsomnolent group at baseline. An interaction between training course and group factors was observed for bedtime, with a significant advance in bedtime between baseline, postintervention 2, and postintervention 3 for the somnolent group. Conclusions: The present study confirms the importance of implementing sleep-hygiene strategies, particularly in athletes with an ESS score ≥11. A conjunction of individual and collective measures (eg, earlier bedtime, napping, and delaying morning training session) could favor the total sleep time achieved.
Edge learning using a fully integrated neuro-inspired memristor chip
Authors: Zhang Wenbin , Yao Peng , Gao Bin , Liu Qi , Wu Dong , Zhang Qingtian , Li Yuankun , Qin Qi , Li Jiaming , Zhu Zhenhua , Cai Yi , Wu Dabin , Tang Jianshi , Qian He , Wang Yu , Wu Huaqiang
Published: September 2023

Learning is highly important for edge intelligence devices to adapt to different application scenes and owners. Current technologies for training neural networks require moving massive amounts of data between computing and memory units, which hinders the implementation of learning on edge devices. We developed a fully integrated memristor chip with the improvement learning ability and low energy cost. The schemes in the STELLAR architecture, including its learning algorithm, hardware realization, and parallel conductance tuning scheme, are general approaches that facilitate on-chip learning by using a memristor crossbar array, regardless of the type of memristor device. Tasks executed in this study included motion control, image classification, and speech recognition.
Presynaptic Ube3a E3 ligase promotes synapse elimination through down-regulation of BMP signaling
Authors: Furusawa Kotaro , Ishii Kenichi , Tsuji Masato , Tokumitsu Nagomi , Hasegawa Eri , Emoto Kazuo
Published: September 2023

Inactivation of the ubiquitin ligase Ube3a causes the developmental disorder Angelman syndrome, whereas increased Ube3a dosage is associated with autism spectrum disorders. Despite the enriched localization of Ube3a in the axon terminals including presynapses, little is known about the presynaptic function of Ube3a and mechanisms underlying its presynaptic localization. We show that developmental synapse elimination requires presynaptic Ube3a activity in
Drosophila
neurons. We further identified the domain of Ube3a that is required for its interaction with the kinesin motor. Angelman syndrome–associated missense mutations in the interaction domain attenuate presynaptic targeting of Ube3a and prevent synapse elimination. Conversely, increased Ube3a activity in presynapses leads to precocious synapse elimination and impairs synaptic transmission. Our findings reveal the physiological role of Ube3a and suggest potential pathogenic mechanisms associated with Ube3a dysregulation.
The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase
Authors: Medoh Uche N. , Hims Andy , Chen Julie Y. , Ghoochani Ali , Nyame Kwamina , Dong Wentao , Abu-Remaileh Monther
Published: September 2023

Lysosomes critically rely on bis(monoacylglycero)phosphate (BMP) to stimulate lipid catabolism, cholesterol homeostasis, and lysosomal function. Alterations in BMP levels in monogenic and complex neurodegeneration suggest an essential function in human health. However, the site and mechanism responsible for BMP synthesis have been subject to debate for decades. Here, we report that the Batten disease gene product CLN5 is the elusive BMP synthase (BMPS). BMPS-deficient cells exhibited a massive accumulation of the BMP synthesis precursor lysophosphatidylglycerol (LPG), depletion of BMP species, and dysfunctional lipid metabolism. Mechanistically, we found that BMPS mediated synthesis through an energy-independent base exchange reaction between two LPG molecules with increased activity on BMP-laden vesicles. Our study elucidates BMP biosynthesis and reveals an anabolic function of late endosomes/lysosomes.
Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease
Authors: Dart Robin J. , Zlatareva Iva , Vantourout Pierre , Theodoridis Efstathios , Amar Ariella , Kannambath Shichina , East Philip , Recaldin Timothy , Mansfield John C. , Lamb Christopher A. , Parkes Miles , Irving Peter M. , Prescott Natalie J. , Hayday Adrian C.
Published: September 2023

Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103
+
γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103
+
Vγ4
+
cell dysregulation and loss were also displayed by humans with germline BTNL3/BTNL8 hypomorphism, which we identified as a risk factor for penetrating Crohn’s disease (CD). Thus, BTNL-dependent selection and/or maintenance of distinct tissue-intrinsic γδ T cells appears to be an evolutionarily conserved axis limiting the progression of a complex, multifactorial, tissue-damaging disease of increasing global incidence.
Songbird species that display more-complex vocal learning are better problem-solvers and have larger brains
Authors: Audet Jean-Nicolas , Couture Mélanie , Jarvis Erich D.
Published: September 2023

Complex vocal learning, a critical component of human spoken language, has been assumed to be associated with more-advanced cognitive abilities. Tests of this hypothesis between individuals within a species have been inconclusive and have not been done across species. In this work, we measured an array of cognitive skills—namely, problem-solving, associative and reversal learning, and self-control—across 214 individuals of 23 bird species, including 19 wild-caught songbird species, two domesticated songbird species, and two wild-caught vocal nonlearning species. We found that the greater the vocal learning abilities of a species, the better their problem-solving skills and the relatively larger their brains. These conclusions held when controlling for noncognitive variables and phylogeny. Our results support a hypothesis of shared genetic and cognitive mechanisms between vocal learning, problem-solving, and bigger brains in songbirds.
Managed retreat or unmanaged disaster
California Against the Sea: Visions for Our Vanishing Coastline
Rosanna Xia
Heyday, 2023. 336 pp.
Authors: Fieseler Clare
Published: September 2023

A journalist offers insight into California’s coastal climate change dilemma
Atomic faulting induced exceptional cryogenic strain hardening in gradient cell–structured alloy
Authors: Pan Qingsong , Yang Muxin , Feng Rui , Chuang Andrew Chihpin , An Ke , Liaw Peter K. , Wu Xiaolei , Tao Nairong , Lu Lei
Published: September 2023

Coarse-grained materials are widely accepted to display the highest strain hardening and the best tensile ductility. We experimentally report an attractive strain hardening rate throughout the deformation stage at 77 kelvin in a stable single-phase alloy with gradient dislocation cells that even surpasses its coarse-grained counterparts. Contrary to conventional understanding, the exceptional strain hardening arises from a distinctive dynamic structural refinement mechanism facilitated by the emission and motion of massive multiorientational tiny stacking faults (planar defects), which are fundamentally distinct from the traditional linear dislocation–mediated deformation. The dominance of atomic-scale planar deformation faulting in plastic deformation introduces a different approach for strengthening and hardening metallic materials, offering promising properties and potential applications.
Albert Eschenmoser (1925–2023)
Authors: Denmark Scott E. , Sorensen Erik J.
Published: September 2023

Organic chemist who demystified the logic of natural product structures
Science needed now, for action
Authors: Kőrösi Csaba , Cullmann Johannes
Published: September 2023

At the beginning of the 77th session of the United Nations General Assembly (UNGA 77) in September 2022, UN members agreed to design and implement solutions to guarantee food, water, and education for all; improve human development; reform the global financial system; secure a healthy environment; and embark on a path toward a less unjust global society. Transformative solutions are needed to respond to the multiple related crises of the Anthropocene and to help reach the Sustainable Development Goals (SDGs). As the 78th session of the UNGA now gets underway, the importance of science in helping the UN to make progress on these issues is as clear and critical as ever. Yet participation of the scientific community is not what it could and needs to be.
In Other Journals
Authors: Simonti Corinne , Fregoso Elisa Collado , Vignieri Sacha , Lopez Bianca , Maroso Mattia , McCartney Melissa , Szuromi Phil
Published: September 2023

Editors’ selections from the current scientific literature
Antarctic meltdown
Authors: Mervis Jeffrey
Published: September 2023

The U.S. Antarctic research program is in trouble, as canceled field seasons imperil data sets and demoralize researchers
Mars Sample Return risks consuming NASA science
Authors: Voosen Paul
Published: September 2023

Forthcoming cost estimate for budget-busting mission could lead to strict caps from Congress
Panel calls for giant boost to space station research
Authors: Greshko Michael
Published: September 2023

Decadal survey says pace of studies should accelerate
Iran prepares to erect a digital wall
Authors: Stone Richard
Published: September 2023

Researchers feel increasingly isolated as government moves to restrict internet access
Broad-spectrum vaccine via combined immunization routes triggers potent immunity to SARS-CoV-2 and its variants
Authors: Xing Man , Wang Yihan , Wang Xinyu , Liu Jiaojiao , Dai Weiqian , Hu Gaowei , He Furong , Zhao Qian , Li Ying , Sun Lingjin , Wang Yuyan , Du Shujuan , Dong Zhongwei , Pang Chongjie , Hu Zhidong , Zhang Xiaoyan , Xu Jianqing , Cai Qiliang , Zhou Dongming
Published: September 2023

Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. Here, we generated a chimpanzee adenoviral vector-based COVID-19 vaccine carrying broad-spectrum immunogens, modified full-length spike, and conserved T-cell epitopes of SARS-CoV-2, and assessed its immune response in mice through intramuscular (i.m.), intranasal (i.n.), or combined immunization routes (i.m. + i.n., or i.n. + i.m.). Compared to other vaccination strategies, the two combined regimens elicited higher neutralizing antibody (NAb) responses to all variants. Compared to i.n. + i.m. regimen, the i.m. + i.n. regimen stimulated a stronger secondary GC response, which is more pivotal to high-quality antibody production than the primary GC response. Moreover, the i.m. + i.n. regimen was adept at mediating systemic cellular immunity, while the i.n. + i .m. regimen tended to elicit lung tissue-resident memory T (T
RM
) cell responses. Overall, the two combined regimens induced comprehensive but distinct immune responses consisting of lgA, lgG, NAbs, GC B cells, long-lived plasma cells, T
RM
cells, and systemic memory T cells, which conferred complete protection against BA.2 infection in hACE2 transgenic mice, and warranted further investigation as potential universal vaccination strategies.

IMPORTANCE

The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.
A gut commensal bacterium promotes black soldier fly larval growth and development partly via modulation of intestinal protein metabolism
Authors: Luo Xingyu , Fang Gangqi , Chen Kuangqin , Song Yu , Lu Tianyi , Tomberlin Jeffery K. , Zhan Shuai , Huang Yongping
Published: September 2023

Black soldier fly (BSF),
Hermetia illucens
(L.) (Diptera: Stratiomyidae), is a promising bio-agent to transform organic wastes into valuable insect biomass, and the intestinal microbes play an essential role in this process. Here, we report that
Citrobacter amalonaticus
, a Gram-negative gut commensal bacterium of BSF larvae, can colonize the whole intestines of the larva and significantly promote the larval growth and development. The bacterial association with the larva had a marked impact on the larval transcriptome and modulated the expression of genes involved in dozens of biological pathways including host macro-nutrient metabolism and immune response. We investigated the underlying mechanisms driving the interaction and found that
C. amalonaticus
association can directly promote the expression of two gene families related to intestinal protein metabolism: Hitryp serine protease trypsin family and Himtp metallopeptidase family. To determine the gene function, we developed a symbiont-mediated double-strand RNA interference approach and successfully achieved gene knockdown in larval midgut
in situ
. Knockdown of the two gene families and protease inhibition in larval intestines attenuated the promoting effects on larval growth significantly. The results indicate that the gut symbiont promotes BSF larval growth partly via modulating the expression of the genes involved in intestinal protein metabolism. Taken together, this study establishes a novel genetic tool to study the insect functional genomics and the host-symbiont interaction and sheds light on the important roles of intestinal protein metabolism on the interaction.

Importance

Black solider fly larvae and the gut microbiota can recycle nutrients from various organic wastes into valuable insect biomass. We found that
Citrobacter amalonaticus
, a gut commensal bacterium of the insect, exerts beneficial effects on larval growth and development and that the expression of many metabolic larval genes was significantly impacted by the symbiont. To identify the larval genes involved in the host-symbiont interaction, we engineered the symbiont to produce double-strand RNA and enabled the strain to silence host genes in the larval gut environment where the interaction takes place. With this approach, we confirmed that two intestinal protease families are involved in the interaction and provided further evidence that intestinal protein metabolism plays a role in the interaction. This work expands the genetic toolkits available to study the insect functional genomics and host-symbiont interaction and provide the prospective for the future application of gut microbiota on the large-scale bioconversion.
Optimization of real-time PCR protocols from lymph node bovine tissue for direct detection of
Mycobacterium tuberculosis
complex
Authors: Vera-Salmoral Eduardo , Gómez-Laguna Jaime , Galán-Relaño Ángela , Ruedas-Torres Inés , Carrasco Librado , Luque Inmaculada , Huerta Belén , Sánchez-Carvajal José María
Published: September 2023

Bovine tuberculosis (bTB) is a zoonotic disease and a global health problem that is subjected to obligatory eradication programs in the European Union. Microbiological culture is an imperfect technique for bTB diagnosis. This study aims to compare and validate two DNA isolation protocols and three different specific DNA targets, IS6110, IS4, and mpb70, to confirm
Mycobacterium tuberculosis
complex (MTC) infection by real-time PCR directly from fresh tissue samples. Fresh lymph node samples were collected from 81 cattle carcasses at the slaughterhouse. A comparison of both extraction protocols was performed with IS
6110
-real-time PCR, showing an adjusted sensitivity (SE) of 78.34% and 95.9% for protocols 1 and 2, respectively, while the specificity (SP) was 100% in both cases. Afterward, the comparison between IS4 and mpb70 targets was performed from the samples extracted with protocol 2, obtaining an adjusted SE of 90.87% and 83.3%, respectively, and an SP of 100% in both cases. The positive likelihood ratio was ∞ for the three targets, and the negative likelihood ratio was 0.04, 0.091, and 0.16 for IS6110, IS4, and mpb70, respectively. Negative predictive values were ≥90%, ≥85%, and ≥80% for real-time PCR targeting IS
6110
, IS4, and mpb70, respectively, when the true prevalence is ≤60%, and the positive predictive value is 100% in any scenario of true prevalence. According to these results, the DNA extraction protocol 2 and real-time PCR targeting IS
6110
or IS4 could be potential first-choice molecular assays to detect MTC directly in fresh bovine tissue samples.

Importance

Bovine tuberculosis (bTB), a chronic infectious and zoonotic disease caused by
Mycobacterium tuberculosis
complex (MTC), is considered a neglected disease of global importance, causing a detrimental impact on public health, particularly in developing countries where tuberculosis remains a major health problem. However, debate around the efficacy of control measures is still an ongoing matter of concern, with poor diagnostic performance being considered one of the most relevant factors involved in the failure to eradicate the disease since many truly infected animals will be misclassified as bTB-free. This study highlights a DNA extraction protocol and real-time PCR targeting IS6110 or IS4 as potential first-choice molecular assays to detect MTC directly in fresh bovine tissue samples, providing rapid, highly sensitive, and specific diagnostic tools as an alternative to microbiology, which could take up to 3 months to complete, shortening the turnaround time for decision makers to be promptly informed.