bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction
Authors: Morishita Yoshikazu , Fuentes Ileana , Gonzalez-Salinas Sofia , Favate John , Mejaes Jennifer , Zushida Ko , Nishi Akinori , Hevi Charles , Goldsmith Noriko , Buyske Steve , Sillivan Stephanie E. , Miller Courtney A. , Kandel Eric R. , Uchida Shusaku , Shah Premal , Alarcon Juan Marcos , Barker David J. , Shumyatsky Gleb P. 
Published: November 2024

AbstractFear extinction leads to a decrease of originally acquired fear responses after the threat is no longer present. Fear extinction is adaptive and critical for organism’s survival, but deficits in extinction may lead to exaggerated fear in animals or post-traumatic stress disorder (PTSD) in humans. Dopamine has recently emerged as essential for fear extinction and PTSD, however the neural circuits serving this dopamine function are only beginning to be investigated, and the dopamine intracellular signaling pathways are unknown. We generated gastrin-releasing peptide gene knockout (Grp-/-) mice and found that they exhibit enhanced fear memory in a stress-enhanced fear learning (SEFL) paradigm, which combines stress exposure and fear extinction, two features critical for developing PTSD. Using in vivo fiber photometry to record dopamine signals, we found that the susceptibility of Grp-/- mice to SEFL is paralleled by an increase in basolateral amygdala (BLA) dopaminergic binding during fear conditioning and early extinction. Combined optogenetics and ex vivo electrophysiology showed an increase in presynaptic ventral tegmental area (VTA)-BLA connectivity in Grp-/- mice, demonstrating a role of dysregulated input from the VTA on BLA function in the absence of the GRP. When examining gene transcription using RNA-seq and qPCR, we discovered concerted down-regulation in dopamine-related genes in the BLA of Grp-/- mice following long-term SEFL memory recall that was not observed in naïve conditions. These experiments demonstrate that the GRP regulates dopamine function in stress-enhanced fear processing and identify the Grp as the first gene known to regulate dopaminergic control of fear extinction.
Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study
Authors: Chan Wing Ching , Liu Lili , Bouras Emmanouil , Zuber Verena , Wen Wanqing , Long Jirong , Gill Dipender , Murphy Neil , Gunter Marc J. , Assimes Themistocles L. , Bujanda Luis , Gruber Stephen B. , Küry Sébastien , Lynch Brigid M. , Qu Conghui , Thomas Minta , White Emily , Woods Michael O. , Peters Ulrike , Li Christopher I. , Chan Andrew T. , Brenner Hermann , Tsilidis Konstantinos K. , Zheng Wei 
Published: November 2024

Abstract
Background
Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.

Methods
Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed.

Results
Genetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02–1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05–1.21) or diabetes (OR = 1.09; 95%CI 1.02–1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets.

Conclusions
We found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.
UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer
Authors: Zhang Le , Ramesh Prashanthi , Atencia Taboada Lidia , Roessler Rebecca , Zijlmans Dick W. , Vermeulen Michiel , Picavet-Havik Daisy I. , van der Wel Nicole N. , Vaz Frédéric M. , Medema Jan Paul 
Published: November 2024

AbstractElevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides. In agreement, lipidomic analysis indicated that sulfatides are strongly reduced in colorectal cancer cells upon treatment with Manidipine-2HCl. Intriguingly, this reduction led to severe mitochondrial swelling and a strong synergism with BH3 mimetics targeting BCL-XL, leading to the activation of mitochondria-dependent apoptosis. Mechanistically, Manidipine-2HCl enhanced mitochondrial BAX localization in a sulfatide-dependent fashion, facilitating its activation by BH3 mimetics. In conclusion, our data indicates that UGT8 mediated synthesis of sulfatides controls mitochondrial homeostasis and BAX localization, dictating apoptosis sensitivity of colorectal cancer cells.
Inhibition of lung tumorigenesis by transient reprogramming in cancer cells
Authors: Pedrosa Pablo , Zhang Zhenguang , Nuñez-Quintela Victor , Macias David , Ge Jianfeng , Denholm Mary , Dyas Anna , Estevez-Souto Valentin , Lado-Fernandez Patricia , Gonzalez Patricia , Gomez Maria , Martin Jose Ezequiel , Da Silva-Alvarez Sabela , Collado Manuel , Muñoz-Espín Daniel 
Published: November 2024

AbstractOncogenic transformation and Oct4, Sox2, Klf4 and c-Myc (OSKM)-mediated induction of pluripotency are two independent and incompatible cellular fates. While continuous expression of OSKM can convert normal somatic cells into teratogenic pluripotent cells, it remains speculative what is the impact of transient OSKM expression in cancer cells. Here, we find that OSKM expression limits the growth of transformed lung cells by inducing apoptosis and senescence. We identify Oct4 and Klf4 as the main individual reprogramming factors responsible for this effect. Mechanistically, the induction of cell cycle inhibitor p21 downstream of the reprogramming factors acts as mediator of cell death and senescence. Using a variety of in vivo systems, including allografts, orthotopic transplantation and KRAS-driven lung cancer mouse models, we demonstrate that transient reprogramming by OSKM expression in cancer cells impairs tumor growth and reduces tumor burden. Altogether, our results show that the induction of transient reprogramming in cancer cells is antitumorigenic opening novel potential therapeutic avenues in oncology.
Effect of individually tailored nutritional counseling on frailty status in older adults with protein-energy malnutrition or risk of it: an intervention study among home care clients
Authors: Kaipainen Tarja , Hartikainen Sirpa , Tiihonen Miia , Nykänen Irma 
Published: November 2024

Abstract
Background
Frailty and protein-energy malnutrition (PEM) are common in older home care clients. In this study, we evaluate the effect of individually tailored dietary counseling on frailty status among home care clients with PEM or its risk aged 75 or older with a follow-up of six months.

Methods
This intervention study is part of the non-randomized population-based Nutrition, Oral Health and Medication (NutOrMed) study in Finland. The frailty was assessed using the abbreviated Comprehensive Geriatric Assessment (aCGA) and included 15 questions from three different domains: cognitive status (MMSE), functional status (ADL, IADL) and depression (GDS-15). The study population consisted of persons with PEM or its risk (intervention group n = 90, control group n = 55). PEM or its risk was defined by MNA score <24 and/or plasma albumin <35 g/l. Registered nutritionist gave individually tailored nutritional counseling for participants at the baseline and nutritional treatment included conventional food items.

Results
The mean age was 83.9 in the intervention and 84.3 in the control group. At the baseline frailty prevalence was 74.4% (n = 67) and after six-month 61.1% (n = 55) in the intervention group and, respectively 74.5% (n = 41) and 80.0% (n = 44) in the control group. The intervention decreased significantly (p < 0.001) the prevalence of frailty in the intervention group, while it increased in the control group.

Conclusions
Individually tailored nutritional counseling reduces the prevalence of frailty among vulnerable home care clients with PEM or its risk. In the nutritional treatment of frailty, adequate intake of protein and energy should be a cornerstone of treatment.
On-chip petahertz electronics for single-shot phase detection
Authors: Ritzkowsky Felix , Yeung Matthew , Bebeti Engjell , Gebert Thomas , Matsuyama Toru , Budden Matthias , Mainz Roland E. , Cankaya Huseyin , Berggren Karl K. , Rossi Giulio Maria , Keathley Phillip D. , Kärtner Franz X. 
Published: November 2024

AbstractAttosecond science has demonstrated that electrons can be controlled on the sub-cycle time scale of an optical waveform, paving the way towards optical frequency electronics. However, these experiments historically relied on high-energy laser pulses and detection not suitable for microelectronic integration. For practical optical frequency electronics, a system suitable for integration and capable of generating detectable signals with low pulse energies is needed. While current from plasmonic nanoantenna emitters can be driven at optical frequencies, low charge yields have been a significant limitation. In this work we demonstrate that large-scale electrically connected plasmonic nanoantenna networks, when driven in concert, enable charge yields sufficient for single-shot carrier-envelope phase detection at repetition rates exceeding tens of kilohertz. We not only show that limitations in single-shot CEP detection techniques can be overcome, but also demonstrate a flexible approach to optical frequency electronics in general, enabling future applications such as high sensitivity petahertz-bandwidth electric field sampling or logic-circuits.
Compression theory for inhomogeneous systems
Authors: Gökmen Doruk Efe , Biswas Sounak , Huber Sebastian D. , Ringel Zohar , Flicker Felix , Koch-Janusz Maciej 
Published: November 2024

AbstractThe physics of complex systems stands to greatly benefit from the qualitative changes in data availability and advances in data-driven computational methods. Many of these systems can be represented by interacting degrees of freedom on inhomogeneous graphs. However, the lack of translational invariance presents a fundamental challenge to theoretical tools, such as the renormalization group, which were so successful in characterizing the universal physical behaviour in critical phenomena. Here we show that compression theory allows the extraction of relevant degrees of freedom in arbitrary geometries, and the development of efficient numerical tools to build an effective theory from data. We demonstrate our method by applying it to a strongly correlated system on an Ammann-Beenker quasicrystal, where it discovers an exotic critical point with broken conformal symmetry. We also apply it to an antiferromagnetic system on non-bipartite random graphs, where any periodicity is absent.
ARMH3 is an ARL5 effector that promotes PI4KB-catalyzed PI4P synthesis at the trans-Golgi network
Authors: Ishida Morié , Golding Adriana E. , Keren-Kaplan Tal , Li Yan , Balla Tamas , Bonifacino Juan S. 
Published: November 2024

AbstractARL5 is a member of the ARF family of small GTPases that is recruited to the trans-Golgi network (TGN) by another ARF-family member, ARFRP1, in complex with the transmembrane protein SYS1. ARL5 recruits its effector, the multisubunit tethering complex GARP, to promote SNARE-dependent fusion of endosome-derived retrograde transport carriers with the TGN. To further investigate the function of ARL5, we sought to identify additional effectors. Using proximity biotinylation and protein interaction assays, we found that the armadillo-repeat protein ARMH3 (C10orf76) binds to active, but not inactive, ARL5, and that it is recruited to the TGN in a SYS1-ARFRP1-ARL5-dependent manner. Unlike GARP, ARMH3 is not required for the retrograde transport of various cargo proteins. Instead, ARMH3 functions to activate phosphatidylinositol 4-kinase IIIβ (PI4KB), accounting for the main pool of phosphatidylinositol 4-phosphate (PI4P) at the TGN. This function contributes to recruitment of the oncoprotein GOLPH3 and glycan modifications at the TGN. These studies thus identify the SYS1-ARFRP1-ARL5-ARMH3 axis as a regulator of PI4KB-dependent generation of PI4P at the TGN.
Strong hole-photon coupling in planar Ge for probing charge degree and strongly correlated states
Authors: De Palma Franco , Oppliger Fabian , Jang Wonjin , Bosco Stefano , Janík Marián , Calcaterra Stefano , Katsaros Georgios , Isella Giovanni , Loss Daniel , Scarlino Pasquale 
Published: November 2024

AbstractSemiconductor quantum dots (QDs) in planar germanium (Ge) heterostructures have emerged as front-runners for future hole-based quantum processors. Here, we present strong coupling between a hole charge qubit, defined in a double quantum dot (DQD) in planar Ge, and microwave photons in a high-impedance (Zr = 1.3 kΩ) resonator based on an array of superconducting quantum interference devices (SQUIDs). Our investigation reveals vacuum-Rabi splittings with coupling strengths up to g0/2π = 260 MHz, and a cooperativity of C ~ 100, dependent on DQD tuning. Furthermore, utilizing the frequency tunability of our resonator, we explore the quenched energy splitting associated with strong Coulomb correlation effects in Ge QDs. The observed enhanced coherence of the strongly correlated excited state signals the presence of distinct symmetries within related spin functions, serving as a precursor to the strong coupling between photons and spin-charge hybrid qubits in planar Ge. This work paves the way towards coherent quantum connections between remote hole qubits in planar Ge, required to scale up hole-based quantum processors.
Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer’s disease
Authors: Slota Jessy A. , Lamoureux Lise , Frost Kathy L. , Sajesh Babu V. , Booth Stephanie A. 
Published: November 2024

AbstractUnderstanding why certain neurons are more sensitive to dysfunction and death caused by misfolded proteins could provide therapeutically relevant insights into neurodegenerative disorders. Here, we harnessed single-cell transcriptomics to examine live neurons isolated from prion-infected female mice, aiming to identify and characterize prion-vulnerable neuronal subsets. Our analysis revealed distinct transcriptional responses across neuronal subsets, with a consistent pathway-level depletion of synaptic gene expression in damage-vulnerable neurons. By scoring neuronal damage based on the magnitude of depleted synaptic gene expression, we identified a diverse spectrum of prion-vulnerable glutamatergic, GABAergic, and medium spiny neurons. Comparison between prion-vulnerable and resistant neurons highlighted baseline gene expression differences that could influence neuronal vulnerability. For instance, the neuroprotective cold-shock protein Rbm3 exhibited higher baseline gene expression in prion-resistant neurons and was robustly upregulated across diverse neuronal classes upon prion infection. We also identified vulnerability-correlated transcripts that overlapped between prion and Alzheimer’s disease. Our findings not only demonstrate the potential of single-cell transcriptomics to identify damage-vulnerable neurons, but also provide molecular insights into neuronal vulnerability and highlight commonalties across neurodegenerative disorders.
Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection
Authors: Kießling Melissa , Cole John J. , Kübel Sabrina , Klein Paulina , Korn Klaus , Henry Amy R. , Laboune Farida , Fourati Slim , Harrer Ellen , Harrer Thomas , Douek Daniel C. , Überla Klaus , Nganou-Makamdop Krystelle 
Published: November 2024

AbstractTo date, our understanding of how HIV infection impacts vaccine-induced cellular immunity is limited. Here, we investigate inflammation, immune activation and antigen-specific T cell responses in HIV-uninfected and antiretroviral-treated HIV-infected people. Our findings highlight lower recall responses of antigen-specific CD4 T cells that correlate with high plasma cytokines levels, T cell hyperactivation and an altered composition of the T subsets enriched with more differentiated cells in the HIV-infected group. Transcriptomic analysis reveals that antigen-specific CD4 T cells of the HIV-infected group have a reduced expression of gene sets previously reported to correlate with vaccine-induced pathogen-specific protective immunity and further identifies a consistent impairment of the IFNα and IFNγ response pathways as mechanism for the functional loss of recall CD4 T cell responses in antiretroviral-treated people. Lastly, in vitro treatment with drugs that reduce inflammation results in higher memory CD4 T cell IFNγ responses. Together, our findings suggest that vaccine-induced cellular immunity may benefit from strategies to counteract inflammation in HIV infection.
Life cycle assessment (LCA) of circular consumer electronics based on IC recycling and emerging PCB assembly materials
Authors: Zhang Tianwei , Bainbridge Andrew , Harwell Jonathon , Zhang Shoushou , Wagih Mahmoud , Kettle Jeff 
Published: November 2024

AbstractAs consumer microelectronics become ever more ubiquitous, there are growing concerns about their environmental impact. However, the diversity of designs and components used in modern devices makes a coherent mitigation strategy hard to formulate. In this work, we perform a quantitative life cycle assessment (LCA) of the environmental profiles of both high-value (a smartwatch) and low-value (a TV remote) devices and find that the optimal mitigation strategy varies substantially between these two extremes. We find that the impact of the smartwatch is dominated by the production costs of its integrated circuits (ICs), and so a priority on device lifetime and design-for-recycling of the ICs is the best path to minimizing impact. On the other hand, the TV remote’s impact is dominated by the cost of its fiberglass (FR4) substrate, with the much simpler ICs playing a much smaller role. Our results show that the impact of low-cost devices is best mitigated by incorporating eco-friendly substrates and additive manufacturing techniques, while also minimizing the use of critical raw materials (CRMs). These results will help guide future industrial strategies, and we provide a list of challenges and opportunities in making electronics green.
Exploring neuropsychiatric symptoms in Friedreich ataxia
Authors: Karamazovova Simona , Stovickova Lucie , Jester Dylan J. , Matuskova Veronika , Paulasova-Schwabova Jaroslava , Kuzmiak Michaela , Zumrova Alena , Andel Ross , Vyhnalek Martin 
Published: November 2024

Abstract
Neuropsychiatric symptoms (NPS) are common in hereditary ataxias as a part of the cerebellar cognitive affective syndrome. In Friedreich ataxia (FRDA), one of the most common hereditary ataxias, depressive symptoms were previously reported, but little is known about other NPS. We aimed to study the presence and severity of a broad range of NPS in individuals with FRDA and assess the relationship between the NPS and the disease severity, cognition, and quality of life and to examine the concordance between the NPS reported by the patients and by their informants. Mild Behavioral Impairment Checklist (MBI-C), a questionnaire designed for screening NPS in the early stages of neurodegenerative diseases, was administered to informants of individuals with FRDA and healthy controls and to people with FRDA themselves. Compared to healthy controls, patients with FRDA scored significantly higher in the total MBI-C score, emotion dysregulation domain (corresponding to depression and anxiety), and decreased motivation domain. When assessed by caregiver, the total MBI-C score and several NPS domains correlated with activities of daily living. Only psychotic symptoms were related to ataxia severity and general cognition. When endorsed by patients, only the relation between few MBI-C domains and quality of life was observed. We found slight to moderate agreement between informant-rated and patient-rated scores. NPS, particularly emotion dysregulation and decreased motivation, are common and clinically relevant in FRDA and should receive more attention due to their potential impact on quality of life and the possibility of therapeutic intervention.
The association between novel urinary kidney damage biomarkers and coronary atherosclerosis in an apparently healthy population
Authors: Lin Yi-Ting , Wuopio Jonas , Larsson Anders , Malinovschi Andrei , Feldreich Tobias , Engström Gunnar , Fall Tove , Ärnlöv Johan 
Published: November 2024

AbstractSeveral novel urinary kidney damage biomarkers predict the progression of kidney disease. However, the relations of these biomarkers to atherosclerosis, a major consequence of kidney disease, are less studied. Urinary levels of several biomarkers, including kidney injury molecule-1 (KIM-1), osteopontin, epidermal growth factor, and Dickkopf-3, were assessed in participants enrolled in the Swedish CArdioPulmonary BioImage Study. The study included 9,628 individuals with a mean age of 57.5 years, of which 52.4% were women. The presence of coronary artery stenosis and the coronary artery calcium score (CACS) were determined using coronary computed tomography angiography. To analyze the associations between coronary atherosclerosis and urinary biomarker levels, an ordered logistic regression model adusting for confounding factors was employed. KIM-1 was the only biomarker associated with both coronary stenosis and CACS after adjusting for established cardiovascular risk factors (odds ratio [95% confidence intervals], 1.23[1.05–1.44] and 1.25[1.07–1.47]). These results were consistent in sensitivity analyses of individuals without hypertension, diabetes, or known cardiovascular disease and with normal kidney function. Urinary KIM-1, a specific marker of proximal tubular damage, was robustly linked to coronary atherosclerosis even in apparently healthy individuals, which suggests that the detrimental interplay between the kidney and cardiovascular system begins before clinically overt kidney disease. Additional studies are warranted to evaluate the urinary KIM-1 to predict kidney and cardiovascular disease.