bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of substrate recognition and translocation by human very long-chain fatty acid transporter ABCD1
Authors: Chen Zhi-Peng , Xu Da , Wang Liang , Mao Yao-Xu , Li Yang , Cheng Meng-Ting , Zhou Cong-Zhao , Hou Wen-Tao , Chen Yuxing 
Published: June 2022

AbstractHuman ABC transporter ABCD1 transports very long-chain fatty acids from cytosol to peroxisome for β-oxidation, dysfunction of which usually causes the X-linked adrenoleukodystrophy (X-ALD). Here, we report three cryogenic electron microscopy structures of ABCD1: the apo-form, substrate- and ATP-bound forms. Distinct from what was seen in the previously reported ABC transporters, the two symmetric molecules of behenoyl coenzyme A (C22:0-CoA) cooperatively bind to the transmembrane domains (TMDs). For each C22:0-CoA, the hydrophilic 3’-phospho-ADP moiety of CoA portion inserts into one TMD, with the succeeding pantothenate and cysteamine moiety crossing the inter-domain cavity, whereas the hydrophobic fatty acyl chain extends to the opposite TMD. Structural analysis combined with biochemical assays illustrates snapshots of ABCD1-mediated substrate transport cycle. It advances our understanding on the selective oxidation of fatty acids and molecular pathology of X-ALD.
The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria
Authors: Uyoga S. , Watson J. A. , Wanjiku P. , Rop J. C. , Makale J. , Macharia A. W. , Kariuki S. N. , Nyutu G. M. , Shebe M. , Mosobo M. , Mturi N. , Rockett K. A. , Woodrow C. J. , Dondorp A. M. , Maitland K. , White N. J. , Williams T. N. 
Published: June 2022

AbstractSevere falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4.
Genome-wide mapping of individual replication fork velocities using nanopore sequencing
Authors: Theulot Bertrand , Lacroix Laurent , Arbona Jean-Michel , Millot Gael A. , Jean Etienne , Cruaud Corinne , Pellet Jade , Proux Florence , Hennion Magali , Engelen Stefan , Lemainque Arnaud , Audit Benjamin , Hyrien Olivier , Le Tallec Benoît 
Published: June 2022

AbstractLittle is known about replication fork velocity variations along eukaryotic genomes, since reference techniques to determine fork speed either provide no sequence information or suffer from low throughput. Here we present NanoForkSpeed, a nanopore sequencing-based method to map and extract the velocity of individual forks detected as tracks of the thymidine analogue bromodeoxyuridine incorporated during a brief pulse-labelling of asynchronously growing cells. NanoForkSpeed retrieves previous Saccharomyces cerevisiae mean fork speed estimates (≈2 kb/min) in the BT1 strain exhibiting highly efficient bromodeoxyuridine incorporation and wild-type growth, and precisely quantifies speed changes in cells with altered replisome progression or exposed to hydroxyurea. The positioning of >125,000 fork velocities provides a genome-wide map of fork progression based on individual fork rates, showing a uniform fork speed across yeast chromosomes except for a marked slowdown at known pausing sites.
Defining TCRγδ lymphoproliferative disorders by combined immunophenotypic and molecular evaluation
Authors: Teramo Antonella , Binatti Andrea , Ciabatti Elena , Schiavoni Gianluca , Tarrini Giulia , Barilà Gregorio , Calabretto Giulia , Vicenzetto Cristina , Gasparini Vanessa Rebecca , Facco Monica , Petrini Iacopo , Grossi Roberto , Pisanti Nadia , Bortoluzzi Stefania , Falini Brunangelo , Tiacci Enrico , Galimberti Sara , Semenzato Gianpietro , Zambello Renato 
Published: June 2022

AbstractTγδ large granular lymphocyte leukemia (Tγδ LGLL) is a rare lymphoproliferative disease, scantily described in literature. A deep-analysis, in an initial cohort of 9 Tγδ LGLL compared to 23 healthy controls, shows that Tγδ LGLL dominant clonotypes are mainly public and exhibit different V-(D)-J γ/δ usage between patients with symptomatic and indolent Tγδ neoplasm. Moreover, some clonotypes share the same rearranged sequence. Data obtained in an enlarged cohort (n = 36) indicate the importance of a combined evaluation of immunophenotype and STAT mutational profile for the correct management of patients with Tγδ cell expansions. In fact, we observe an association between Vδ2/Vγ9 clonality and indolent course, while Vδ2/Vγ9 negativity correlates with symptomatic disease. Moreover, the 7 patients with STAT3 mutations have neutropenia and a CD56-/Vδ2- phenotype, and the 3 cases with STAT5B mutations display an asymptomatic clinical course and CD56/Vδ2 expression. All these data indicate that biological characterization is needed for Tγδ-cell neoplasm definition.
Transforming Ti3C2Tx MXene’s intrinsic hydrophilicity into superhydrophobicity for efficient photothermal membrane desalination
Authors: Zhang Baoping , Wong Pak Wai , Guo Jiaxin , Zhou Yongsen , Wang Yang , Sun Jiawei , Jiang Mengnan , Wang Zuankai , An Alicia Kyoungjin 
Published: June 2022

AbstractOwing to its 100% theoretical salt rejection capability, membrane distillation (MD) has emerged as a promising seawater desalination approach to address freshwater scarcity. Ideal MD requires high vapor permeate flux established by cross-membrane temperature gradient (∆T) and excellent membrane durability. However, it’s difficult to maintain constant ∆T owing to inherent heat loss at feedwater side resulting from continuous water-to-vapor transition and prevent wetting transition-induced membrane fouling and scaling. Here, we develop a Ti3C2Tx MXene-engineered membrane that imparts efficient localized photothermal effect and strong water-repellency, achieving significant boost in freshwater production rate and stability. In addition to photothermal effect that circumvents heat loss, high electrically conductive Ti3C2Tx MXene also allows for self-assembly of uniform hierarchical polymeric nanospheres on its surface via electrostatic spraying, transforming intrinsic hydrophilicity into superhydrophobicity. This interfacial engineering renders energy-efficient and hypersaline-stable photothermal membrane distillation with a high water production rate under one sun irradiation.
Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts
Authors: Petropoulou-Vathi Lilian , Simitsi Athina , Valkimadi Politymi-Eleni , Kedariti Maria , Dimitrakopoulos Lampros , Koros Christos , Papadimitriou Dimitra , Papadimitriou Alexandros , Stefanis Leonidas , Alcalay Roy N. , Rideout Hardy J. 
Published: June 2022

AbstractDespite several advances in the field, pharmacodynamic outcome measures reflective of LRRK2 kinase activity in clinical biofluids remain urgently needed. A variety of targets and approaches have been utilized including assessments of LRRK2 itself (levels, phosphorylation), or its substrates (e.g. Rab10 or other Rab GTPases). We have previously shown that intrinsic kinase activity of LRRK2 isolated from PBMCs of G2019S carriers is elevated, irrespective of disease status. In the present study we find that phosphorylation of Rab10 is also elevated in G2019S carriers, but only those with PD. Additionally, phosphorylation of this substrate is also elevated in two separate idiopathic PD cohorts, but not in carriers of the A53T mutation in α-synuclein. In contrast, Rab29 phosphorylation was specifically reduced in urinary exosomes from A53T and idiopathic PD patients. Taken together, our findings highlight the need for the assessment of multiple complimentary targets for a more comprehensive picture of the disease.
A repeating fast radio burst associated with a persistent radio source
Authors: Niu C.-H. , Aggarwal K. , Li D. , Zhang X. , Chatterjee S. , Tsai C.-W. , Yu W. , Law C. J. , Burke-Spolaor S. , Cordes J. M. , Zhang Y.-K. , Ocker S. K. , Yao J.-M. , Wang P. , Feng Y. , Niino Y. , Bochenek C. , Cruces M. , Connor L. , Jiang J.-A. , Dai S. , Luo R. , Li G.-D. , Miao C.-C. , Niu J.-R. , Anna-Thomas R. , Sydnor J. , Stern D. , Wang W.-Y. , Yuan M. , Yue Y.-L. , Zhou D.-J. , Yan Z. , Zhu W.-W. , Zhang B. 
Published: June 2022

AbstractThe dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately $${903}_{-111}^{+72}$$

903

−
111

+
72

parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.
Direct measurement of the 3He+ magnetic moments
Authors: Schneider A. , Sikora B. , Dickopf S. , Müller M. , Oreshkina N. S. , Rischka A. , Valuev I. A. , Ulmer S. , Walz J. , Harman Z. , Keitel C. H. , Mooser A. , Blaum K. 
Published: June 2022

AbstractHelium-3 has nowadays become one of the most important candidates for studies in fundamental physics1–3, nuclear and atomic structure4,5, magnetometry and metrology6, as well as chemistry and medicine7,8. In particular, 3He nuclear magnetic resonance (NMR) probes have been proposed as a new standard for absolute magnetometry6,9. This requires a high-accuracy value for the 3He nuclear magnetic moment, which, however, has so far been determined only indirectly and with a relative precision of 12 parts per billon10,11. Here we investigate the 3He+ ground-state hyperfine structure in a Penning trap to directly measure the nuclear g-factor of 3He+$${g}_{I}^{{\prime} }=-\,4.2550996069(30{)}_{{\rm{stat}}}(17{)}_{{\rm{sys}}}$$

g

I

′

=
−

4.2550996069
(
30

)

stat

(
17

)

sys

, the zero-field hyperfine splitting $${E}_{{\rm{HFS}}}^{\exp }=-\,8,\,665,\,649,\,865.77{(26)}_{{\rm{stat}}}{(1)}_{{\rm{sys}}}$$

E

HFS

exp

=
−

8
,

665
,

649
,

865.77

(

26

)

stat

(
1
)

sys

Hz and the bound electron g-factor $${g}_{e}^{{\rm{\exp }}}=-\,2.00217741579(34{)}_{{\rm{stat}}}(30{)}_{{\rm{sys}}}$$

g

e

exp

=
−

2.00217741579
(
34

)

stat

(
30

)

sys

. The latter is consistent with our theoretical value $${g}_{e}^{{\rm{theo}}}=-\,2.00217741625223(39)$$

g

e

theo

=
−

2.00217741625223
(
39
)

based on parameters and fundamental constants from ref. 12. Our measured value for the 3He+ nuclear g-factor enables determination of the g-factor of the bare nucleus $${g}_{I}=-\,4.2552506997(30{)}_{{\rm{stat}}}(17{)}_{{\rm{sys}}}(1{)}_{{\rm{theo}}}$$

g

I

=
−

4.2552506997
(
30

)

stat

(
17

)

sys

(
1

)

theo

via our accurate calculation of the diamagnetic shielding constant13$${\sigma }_{{}^{3}{\mathrm{He}}^{+}}=0.00003550738(3)$$

σ

3

He

+

=
0.00003550738

(
3
)

. This constitutes a direct calibration for 3He NMR probes and an improvement of the precision by one order of magnitude compared to previous indirect results. The measured zero-field hyperfine splitting improves the precision by two orders of magnitude compared to the previous most precise value14 and enables us to determine the Zemach radius15 to $${r}_{Z}=2.608(24)$$

r

Z

=
2.608
(
24
)

fm.
Potentiating adoptive cell therapy using synthetic IL-9 receptors
Authors: Kalbasi Anusha , Siurala Mikko , Su Leon L. , Tariveranmoshabad Mito , Picton Lora K. , Ravikumar Pranali , Li Peng , Lin Jian-Xin , Escuin-Ordinas Helena , Da Tong , Kremer Sarah V. , Sun Amy L. , Castelli Sofia , Agarwal Sangya , Scholler John , Song Decheng , Rommel Philipp C. , Radaelli Enrico , Young Regina M. , Leonard Warren J. , Ribas Antoni , June Carl H. , Garcia K. Christopher 
Published: June 2022

AbstractSynthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning chemotherapy1,2. Here we designed chimeric receptors that have an orthogonal IL-2 receptor extracellular domain (ECD) fused with the intracellular domain (ICD) of receptors for common γ-chain (γc) cytokines IL-4, IL-7, IL-9 and IL-21 such that the orthogonal IL-2 cytokine elicits the corresponding γccytokine signal. Of these, T cells that signal through the chimeric orthogonal IL-2Rβ-ECD–IL-9R-ICD (o9R) are distinguished by the concomitant activation of STAT1, STAT3 and STAT5 and assume characteristics of stem cell memory and effector T cells. Compared to o2R T cells, o9R T cells have superior anti-tumour efficacy in two recalcitrant syngeneic mouse solid tumour models of melanoma and pancreatic cancer and are effective even in the absence of conditioning lymphodepletion. Therefore, by repurposing IL-9R signalling using a chimeric orthogonal cytokine receptor, T cells gain new functions, and this results in improved anti-tumour activity for hard-to-treat solid tumours.
Cohesin-mediated loop anchors confine the locations of human replication origins
Authors: Emerson Daniel J. , Zhao Peiyao A. , Cook Ashley L. , Barnett R. Jordan , Klein Kyle N. , Saulebekova Dalila , Ge Chunmin , Zhou Linda , Simandi Zoltan , Minsk Miriam K. , Titus Katelyn R. , Wang Weitao , Gong Wanfeng , Zhang Di , Yang Liyan , Venev Sergey V. , Gibcus Johan H. , Yang Hongbo , Sasaki Takayo , Kanemaki Masato T. , Yue Feng , Dekker Job , Chen Chun-Long , Gilbert David M. , Phillips-Cremins Jennifer E. 
Published: June 2022

AbstractDNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability1,2. At present, it is unknown how the locations of replication origins are determined in the human genome. Here we dissect the role of topologically associating domains (TADs)3–6, subTADs7 and loops8 in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase.
Important marine areas for endangered African penguins before and after the crucial stage of moulting
Authors: Carpenter-Kling Tegan , de Blocq Andrew , Hagen Christina , Harding Craig , Morris Taryn , Pichegru Lorien , Roberts Jennifer , Ryan Peter G. , Wanless Ross M. , McInnes Alistair 
Published: June 2022

AbstractThe population of the Endangered African penguinSpheniscus demersushas decreased by > 65% in the last 20 years. A major driver of this decrease has been the reduced availability of their principal prey, sardineSardinops sagaxand anchovyEngraulis encrasicolus.To date, conservation efforts to improve prey availability have focused on spatial management strategies to reduce resource competition with purse-seine fisheries during the breeding season. However, penguins also undergo an annual catastrophic moult when they are unable to feed for several weeks. Before moulting they must accumulate sufficient energy stores to survive this critical life-history stage. Using GPS tracking data collected between 2012 and 2019, we identify important foraging areas for pre- and post-moult African penguins at three of their major colonies in South Africa: Dassen Island and Stony Point (Western Cape) and Bird Island (Eastern Cape). The foraging ranges of pre- and post-moult adult African penguins (c. 600 km from colony) was far greater than that previously observed for breeding penguins (c. 50 km from colony) and varied considerably between sites, years and pre- and post-moult stages. Despite their more extensive range during the non-breeding season, waters within 20 and 50 km of their breeding colonies were used intensively and represent important foraging areas to pre- and post-moult penguins. Furthermore, penguins in the Western Cape travelled significantly further than those in the Eastern Cape which is likely a reflection of the poor prey availability along the west coast of South Africa. Our findings identify important marine areas for pre- and post-moult African penguins and support for the expansion of fisheries-related spatio-temporal management strategies to help conserve African penguins outside the breeding season.
ADHD symptoms and use of anabolic androgenic steroids among male weightlifters
Authors: Kildal Emilie , Hassel Bjørnar , Bjørnebekk Astrid 
Published: June 2022

AbstractUse of anabolic androgenic steroids (AAS) is associated with adverse health effects. The factors that predispose to AAS use among athletes are poorly understood, but attention deficit/hyperactivity disorder (ADHD), which is known to occur among athletes more often than in the general population, is associated with risk behaviors, including substance abuse. We aimed to see if AAS use in male weightlifters was associated with ADHD symptoms, and test the link between ADHD symptoms and cognitive performance. Hundred and forty male weightlifters, 72 AAS users and 68 weightlifting controls (WLC), completed the Achenbach system of empirically based assessment (ASEBA) for ADHD symptoms and underwent cognitive examination. Self-reported ADHD symptom scores were significantly higher among AAS users compared to WLC, and scores in the range indicating clinically important ADHD was significantly more common in the AAS-using group. Age of onset of AAS use correlated inversely with ADHD scale score (r = − 0.35; p = 0.003). ADHD score correlated inversely with cognitive scores for working memory (r = − 0.25, p < 0.001), processing speed (r = − 0.24, p < 0.001), verbal learning and memory (r = − 0.19, p = 0.03), and problem solving (r = − 0.20, p = 0.02). AAS use among weightlifters is associated with ADHD symptoms and corresponding lower cognitive performance. Recognising a relationship between ADHD symptoms and AAS use may guide drug prevention strategies in sports.
Transient dynamics of a single molecular transistor in the presence of local electron–phonon and electron–electron interactions and quantum dissipation
Authors: Kalla Manasa , Chebrolu Narasimha Raju , Chatterjee Ashok 
Published: June 2022

AbstractWe consider a single molecular transistor in which a quantum dot with local electron–electron and electron–phonon interactions is coupled to two metallic leads, one of which acts like a source and the other like a drain. The system is modeled by the Anderson-Holstein (AH) model. The quantum dot is mounted on a substrate that acts as a heat bath. Its phonons interact with the quantum dot phonons by the Caldeira–Leggett interaction giving rise to dissipation in the dynamics of the quantum dot system. A simple canonical transformation exactly treats the interaction of the quantum dot phonons with the substrate phonons. The electron–phonon interaction of the quantum dot is eliminated by the celebrated Lang-Firsov transformation. The time-dependent current is finally calculated by the Keldysh Green function technique with various types of bias. The transient-time phase diagram is analysed as a function of the system parameters to explore regions that can be used for fast switching in devices like nanomolecular switches.
Optimal self-assembly of lipid nanoparticles (LNP) in a ring micromixer
Authors: Ripoll Manon , Martin Elian , Enot Mathilde , Robbe Oscar , Rapisarda Chiara , Nicolai Marie-Claire , Deliot Aurélie , Tabeling Patrick , Authelin Jean-René , Nakach Mostafa , Wils Pierre 
Published: June 2022

AbstractLipid nanoparticles (LNPs) for RNA and DNA delivery have attracted considerable attention for their ability to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality, low-stress conditions, and fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow rates, a degradation in performance in terms of size, monodispersity and encapsulation efficiency. In this study, we focus on the ring micromixer, which is well adapted to high throughput. We reveal three regimes, side-by-side, transitional and highly mixed, that control the mixing performance of the device. Furthermore, using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We emphasize the importance of the flow-rate ratio and propose a physical criterion based on the onset of temporal instabilities for producing LNPs with optimal characteristics in terms of geometry, monodispersity and encapsulation yield. These criteria are generally applicable.