bluuebunny/crossref_metadata_2025 huggingface dataset:
Between a Rock and a Hard Place: How Kazakhstan's Civil Society Navigates Precarity
Authors: Wood Colleen
Published: August 2023

What forms of precarity do civil society actors experience in Central Asia? What are the sources of these precarities? In this article, I synthesize literature from political science and development studies to identify five top-down mechanisms of precaritization for civil society: (extra)legal restrictions on operations, financing activities, flows of funding from the Global North, professionalization, and the sociopolitical atmosphere. I draw on twenty-seven interviews with activists and human rights defenders in Kazakhstan to consider how civil society actors navigate structural constraints on their work. In line with the literature on authoritarian regimes, I find that civil society actors who criticize the regime face precarity through coercion and bureaucratic demands. But whereas development studies scholarship has been pessimistic about the effects of professionalization, Kazakhstan's civil society actors see their technical training and pressure to formalize their organizations as beneficial to their reputation and institutional leverage.
Surgical treatment of anomalous right upper lobe pulmonary vein obstruction caused by compression between pulmonary artery and trachea: a case report
Authors: Zhang Benqing , Xia Jianming , Wang Xiaoqi
Published: August 2023

The normal anatomical course of right upper lobe pulmonary vein involves drainage anteriorly to the pulmonary artery, ultimately reaching the left atrium. However, anomalies can occur with the most common variation involving the convergence of the right upper lobe pulmonary vein with the superior vena cava. In a rare pulmonary vascular malformation, the anomalous right upper lobe pulmonary vein takes a path between the right pulmonary artery and right main bronchus [1]. During a clinical consultation, a patient presented in our hospital with this specific anomalous right upper lobe pulmonary vein, along with an atrial septal defect and a patent ductus arteriosus. As a consequence of this aberrant positioning, the right upper lobe pulmonary vein was compressed between the pulmonary artery and trachea, leading to pulmonary vein obstruction. Thus, a successful pulmonary vein replantation was performed to correct the congenital malformation.
“RISE AND FALL” OF THE WALRASIAN PROGRAM IN ECONOMICS: A SOCIAL AND INTELLECTUAL DYNAMICS OF THE GENERAL EQUILIBRIUM THEORY
Authors: Kirtchik Olessia , Boldyrev Ivan
Published: August 2023

This paper aims at understanding social practices and institutions that ensured the transnational diffusion, recognition, and renewal of the research program in the General Equilibrium Theory (GET), in spite of multiple critics and apparent theoretical dead ends. First, we trace the main conceptual developments of the Walrasian GET program since the 1950s and thus elaborate on its intellectual identity. Then, based on a systematic study of the educational and professional trajectories typical for several generations of GET scholars, we analyze a social form taken by this transnational and multidisciplinary “scientific community”: an institutional dynamics of the Walrasian GET program, most common career patterns, and the forms of international and intergenerational transmission. We construct a database of GET theorists and apply to this dataset a technique of Multiple Correspondence Analysis (MCA) in order to investigate the relational patterns between attribution of scientific credit (symbolic capital) and biographical properties in a transnational space of the GET scholars.
A randomised controlled school-based nutritional intervention in five Middle Eastern countries: Ajyal Salima improved students’ dietary and physical activity habits
Authors: Habib-Mourad Carla , Maliha Carla , Kassis Amira , Nguyen Anh Thi , Ammar Diala , Haji Eman , AlTarazi Lina , Totah Suzanne , Hwalla Nahla
Published: August 2023

Objective:

The purpose of this study was to measure the impact of the Ajyal Salima school intervention on nutrition and physical activity outcomes in children aged 9–11 years.

Design:

The study was a 1-year cluster-randomised controlled trial. Ajyal Salima used a multi-component approach including classroom activities, family programme and food service adaptation. Outcomes included daily intake of breakfast, frequency of healthy and unhealthy food consumption, frequency of physical activity, knowledge score and self-efficacy score. Intervention and control groups were compared for all main outcomes and a post-intervention qualitative evaluation assessed strengths and limitations of the intervention components.

Setting:

Schools in five countries – Lebanon, Jordan, Palestine, Saudi Arabia and Bahrain.

Participants:

Schools were selected by Ministries of Health and Education within their jurisdictions. Forty-five intervention schools (6052 students) and forty-six control schools (6200 students) were included in the analysis.

Results:

The intervention group had a significantly higher odds of consuming breakfast daily (OR 95 % CI = 1·60, 1·35, 1·90), consuming healthy foods (OR 95 % CI = 1·60, 1·39, 1·84) and a decreased odds of consuming unhealthy foods and sweetened beverages (OR, 95 % CI = 0·70, 0·60, 0·81). Additionally, school children in the intervention group, as compared with the control group, were 47 % more likely to exercise outside school hours (OR 95 % CI = 1·47, 1·23, 1·76). Lastly, children in the intervention group had a significantly improved nutritional knowledge score and improved self-efficacy by 1·3 score unit and 1·1 score unit, respectively.

Conclusions:

The Ajyal Salima intervention led to significant improvements in dietary and physical activity habits among school children and increased nutritional knowledge scores.
Becoming a Virtuosa: Advice from Vienna, 1769
Authors: Beesley Clare
Published: August 2023

First-hand accounts explaining how a young British virtuosa went about establishing an international career in the later eighteenth century are scant. However, a previously unstudied handwritten page contained within the Rackett Family of Spettisbury Archive at the Dorset History Centre provides new insights into this underexplored area. In this article, I examine an anonymous 1769 document entitled ‘a Vienne’ from which the guiding voices of eminent musicians at the Vienna court, including Johann Adolf Hasse, Faustina Bordoni, Marianna Martines and their circle, emerge. I argue that this item is in fact an aide-mémoire memorializing intimate glimpses of private conversations, career-shaping advice and impressions that helped mould its author into a virtuosa. Further, by means of palaeographical and biographical evidence I identify the author as the young British glass-armonica player Marianne Davies and assert that her recollections, preserved in this hitherto overlooked piece of ephemera, reconstruct how the educational process of becoming a virtuosa took place.
The Making of Jamaica's ‘First Composer’: Rethinking Samuel Felsted
Authors: Weaver Wayne
Published: August 2023

This article examines the links between the music of Anglo-Jamaican organist and composer Samuel Felsted (1743–1802) and his environment of late eighteenth-century Kingston, building on research published since the 1980s. Although Felsted, a person of English-American heritage who was born in Jamaica, was part of the island's European-origin community, most of his local contemporaries were people of African descent. Like many of his friends, family members and acquaintances, Felsted was a slave owner, and, as I argue here, his various literary and artistic outputs demonstrate how he was influenced by the kinds of issues – such as slavery, servitude, sovereignty and nationhood – that surfaced in the public and private discourses of his time. Considering what Felsted's cultural legacy might mean today, I turn to his undated and virtually unknown oratorio The Dedication, for which he wrote both the text and the music. The Dedication contains literary themes that allow its connections to Felsted's world and its setting of ancient Babylon to be explored. I also suggest the early 1790s as a possible time of composition for this work.
Konstrukt- und Kriteriumsvalidität der neuropsychologischen Testbatterien TAP und KiTAP bei Kindern im Grundschulalter
Authors: Reissmann Andreas , Kaunzinger Ivo , Lange Klaus W.
Published: August 2023

Zusammenfassung: Trotz der Verbreitung der „Testbatterie zur Aufmerksamkeitsprüfung“ (TAP) sowie deren Kinderversion (KiTAP) fehlen Studien zur konvergenten und kriteriumsbezogenen Validität beider Verfahren. Grundschulkinder im Alter von 8 bis 11 Jahren ( N = 99) bearbeiteten korrespondierende Untertests beider Testbatterien. Zusätzlich wurden Testmotivation sowie Schulnoten erhoben. Die Korrelationen zwischen beiden Testbatterien waren gering, diesbezügliche Normwertvergleiche zeigten signifikante Unterschiede. Aus den Analysen zur Testmotivation ergab sich ein Vorteil für die KiTAP. Leistungsparameter beider Testbatterien korrelierten nur schwach mit Schulnoten. Die Ergebnisse stellen im Grundschulalter Reliabilität und Validität sowie die Güte der Testnormierung beider Verfahren infrage. In der diagnostischen Praxis bei Kindern sollten mit TAP und KiTAP erhobene Untersuchungsbefunde nur mit Vorsicht interpretiert werden, da je nach verwendetem Verfahren unterschiedliche Befunde zu erwarten sind.
Energetic Neutral Atom (ENA) Emission Characteristics at the Moon and Mercury From 3D Regolith Simulations of Solar Wind Reflection
Authors: Szabo P. S. , Poppe A. R. , Mutzke A. , Fatemi S. , Vorburger A. , Wurz P.
Published: August 2023

The reflection of solar wind protons as energetic neutral atoms (ENAs) from the lunar surface has regularly been used to study the plasma‐surface interaction at the Moon. However, there still exists a fundamental lack of knowledge of the scattering process. ENA emission from the surface is expected to similarly occur at Mercury and will be studied by BepiColombo. Understanding this solar wind backscattering will allow studies of both Mercury's plasma environment as well as properties of the hermean surface itself. Here, we expand on previous simulation studies of the solar‐wind‐regolith interaction with 3D grains in SDTrimSP‐3D to compare the predicted scattering energies and angles to ENA measurements from the Moon by the Chandrayaan‐1 and IBEX missions. The simulations reproduce a backward emission toward the Sun, which can be connected to the geometry of the regolith grain stacking. In contrast, the ENA energy distribution and its Maxwellian shape is mostly connected to the solar wind velocity. Our simulations also correctly describe a lunar ENA albedo between 10% and 20% and support its decrease with solar wind velocity. We further expand our studies to illustrate how BepiColombo will be able to observe ENAs at Mercury using hybrid simulations of Mercury's magnetosphere as an input for the complex surface precipitation patterns. We demonstrate that the variable ion precipitation will directly influence ENA emission from the surface. The orbits of BepiColombo's Mercury Planetary Orbiter and Mercury Magnetospheric Orbiter/Mio spacecraft are shown to be suitable to observe ENA emission patterns both on a local and a global scale.
Deciduous Tundra Shrubs Shift Toward More Acquisitive Light Absorption Strategy Under Climate Change Treatments
Authors: Heim R. J. , Iturrate‐Garcia M. , Reji Chacko M. , Karsanaev S. , Maximov T. C. , Heijmans M. M. P. D. , Schaepman‐Strub G.
Published: August 2023

The effects of climate change on plants are particularly pronounced in the Arctic region. Warming relaxes the temperature and nutrients boundaries that limit tundra plant growth. Increased resource availability under future climate conditions may induce a shift from a conservative economic strategy to an acquisitive one. Following the leaf economics spectrum that hypothesizes a strategy gradient between survival, plant size and costs for the photosynthetic leaf area, light absorption of tundra plants may increase. We investigated climate change effects on light absorptance and the relationship between light absorptance (fraction of absorbed photosynthetically active radiation, FAPAR) and structural and nutritional leaf traits, performing a soil warming and surface soil fertilization experiment on two deciduous tundra shrub species. Our results show that fertilization and warming combined increase light absorptance in Arctic shrubs and that FAPAR is correlated with leaf nutrients but not with structural leaf traits. This indicates an economic strategy shift of shrubs from conservative to acquisitive induced by warming and fertilization combined. We found species‐specific differences: FAPAR was influenced by warming alone in Betula nana but not in Salix pulchra, and FAPAR was correlated with leaf phosphorus in B. nana but not in S. pulchra. We attribute this to water limitation of B. nana that generally grows in drier areas within the study site compared to S. pulchra. We conclude that FAPAR is a measure that opens up more possibilities to estimate nutritional leaf traits and nutrient cycles, plant economic strategies, and ecological feedbacks of the tundra ecosystem on broader scales.
Phonon engineering in Yb:La2CaB10O19 crystal for extended lasing beyond the fluorescence spectrum
Authors: Cheng Yanling , Liang Fei , Lu Dazhi , Feng Jingcheng , Zhang Guochun , Yu Haohai , Zhang Huaijin , Wu Yicheng
Published: August 2023

Since the first invention of the laser in 1960, direct lasing outside the fluorescence spectrum is deemed impossible owing to the “zero-gain” cross-section. However, when electron-phonon coupling meets laser oscillation, an energy modulation by the quantized phonon can tailor the electronic transitions, thus directly creating some unprecedented lasers with extended wavelengths by phonon engineering. Here, we demonstrate a broadband lasing (1000–1280 nm) in a Yb-doped La2CaB10O19 (Yb:LCB) crystal, far beyond its spontaneous fluorescence spectrum. Numerical calculations and in situ Raman verify that such a substantial laser emission is devoted to the multiphonon coupling to lattice vibrations of a dangling “quasi-free-oxygen” site, with the increasing phonon numbers step-by-step (n = 1–6). This new structural motif provides more alternative candidates with strong-coupling laser materials. Moreover, the quantitative relations between phonon density distribution and laser wavelength extension are discussed. These results give rise to the search for on-demand lasers in the darkness and pave a reliable guideline to study those intriguing electron-phonon-photon coupled systems for integrated photonic applications.
Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia
Authors: Saleh Y. , Jarratt-Barnham I. , Petitet P. , Fernandez-Egea E. , Manohar S. G. , Husain M.
Published: August 2023

Background

Motivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia.

Methods

Forty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed.

Results

Overall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter.

Conclusion

Motivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.
N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via β-catenin/MYC/LDHA axis mediated glycolytic reprogramming
Authors: Zhou Mingxia , He Jing , Li Yingxia , Jiang Libin , Ran Jiaxuan , Wang Chang , Ju Chenxi , Du Dan , Xu Xinyu , Wang Xuexin , Li Hongle , He Fucheng , Wen Hongtao
Published: August 2023

Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients’ lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via β-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/β-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/β-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.
The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling
Authors: Shi Jian , Miao Daojia , Lv Qingyang , Wang Keshan , Wang Qi , Liang Huageng , Yang Hongmei , Xiong Zhiyong , Zhang Xiaoping
Published: August 2023

Metabolic reprogramming is a hallmark of cancer, and the impact of lipid metabolism as a crucial aspect of metabolic reprogramming on clear cell renal cell carcinoma (ccRCC) progression has been established. However, the regulatory mechanisms underlying the relationship between metabolic abnormalities and ccRCC progression remain unclear. Therefore, this study aimed to identify key regulatory factors of metabolic reprogramming in ccRCC and provide potential therapeutic targets for ccRCC patients. Potential metabolic regulatory factors in ccRCC were screened using bioinformatics analysis. Public databases and patient samples were used to investigate the aberrant expression of Oxoglutarate dehydrogenase-like (OGDHL) in ccRCC. The function of OGDHL in ccRCC growth and metastasis was evaluated through in vitro and in vivo functional experiments. Mechanistic insights were obtained through luciferase reporter assays, chromatin immunoprecipitation, RNA methylation immunoprecipitation, and mutagenesis studies. OGDHL mRNA and protein levels were significantly downregulated in ccRCC tissues. Upregulation of OGDHL expression effectively inhibited ccRCC growth and metastasis both in vitro and in vivo. Furthermore, FTO-mediated OGDHL m6A demethylation suppressed its expression in ccRCC. Mechanistically, low levels of OGDHL promoted TFAP2A expression by inhibiting ubiquitination levels, which then bound to the FASN promoter region and transcriptionally activated FASN expression, thereby promoting lipid accumulation and ERK pathway activation. Our findings demonstrate the impact of OGDHL on ccRCC progression and highlight the role of the FTO/OGDHL/TFAP2A/FASN axis in regulating ccRCC lipid metabolism and progression, providing new targets for ccRCC therapy.
Prominent Josephson tunneling between twisted single copper oxide planes of Bi2Sr2-xLaxCuO6+y
Authors: Wang Heng , Zhu Yuying , Bai Zhonghua , Wang Zechao , Hu Shuxu , Xie Hong-Yi , Hu Xiaopeng , Cui Jian , Huang Miaoling , Chen Jianhao , Ding Ying , Zhao Lin , Li Xinyan , Zhang Qinghua , Gu Lin , Zhou X. J. , Zhu Jing , Zhang Ding , Xue Qi-Kun
Published: August 2023

Josephson tunneling in twisted cuprate junctions provides a litmus test for the pairing symmetry, which is fundamental for understanding the microscopic mechanism of high temperature superconductivity. This issue is rekindled by experimental advances in van der Waals stacking and the proposal of an emergent d+id-wave. So far, all experiments have been carried out on Bi2Sr2CaCu2O8+x (Bi-2212) with double CuO2 planes but show controversial results. Here, we investigate junctions made of Bi2Sr2-xLaxCuO6+y (Bi-2201) with single CuO2 planes. Our on-site cold stacking technique ensures uncompromised crystalline quality and stoichiometry at the interface. Junctions with carefully calibrated twist angles around 45° show strong Josephson tunneling and conventional temperature dependence. Furthermore, we observe standard Fraunhofer diffraction patterns and integer Fiske steps in a junction with a twist angle of 45.0±0.2°. Together, these results pose strong constraints on the d or d+id-wave pairing and suggest an indispensable isotropic pairing component.
Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression
Authors: Bailey Peter , Ridgway Rachel A. , Cammareri Patrizia , Treanor-Taylor Mairi , Bailey Ulla-Maja , Schoenherr Christina , Bone Max , Schreyer Daniel , Purdie Karin , Thomson Jason , Rickaby William , Jackstadt Rene , Campbell Andrew D. , Dimonitsas Emmanouil , Stratigos Alexander J. , Arron Sarah T. , Wang Jun , Blyth Karen , Proby Charlotte M. , Harwood Catherine A. , Sansom Owen J. , Leigh Irene M. , Inman Gareth J.
Published: August 2023

The molecular basis of disease progression from UV-induced precancerous actinic keratosis (AK) to malignant invasive cutaneous squamous cell carcinoma (cSCC) and potentially lethal metastatic disease remains unclear. DNA sequencing studies have revealed a massive mutational burden but have yet to illuminate mechanisms of disease progression. Here we perform RNAseq transcriptomic profiling of 110 patient samples representing normal sun-exposed skin, AK, primary and metastatic cSCC and reveal a disease continuum from a differentiated to a progenitor-like state. This is accompanied by the orchestrated suppression of master regulators of epidermal differentiation, dynamic modulation of the epidermal differentiation complex, remodelling of the immune landscape and an increase in the preponderance of tumour specific keratinocytes. Comparative systems analysis of human cSCC coupled with the generation of genetically engineered murine models reveal that combinatorial sequential inactivation of the tumour suppressor genesTgfbr2,Trp53, andNotch1coupled with activation of Ras signalling progressively drives cSCC progression along a differentiated to progenitor axis. Taken together we provide a comprehensive map of the cSCC disease continuum and reveal potentially actionable events that promote and accompany disease progression.
Architecture of the Heme-translocating CcmABCD/E complex required for Cytochrome c maturation
Authors: Ilcu Lorena , Denkhaus Lukas , Brausemann Anton , Zhang Lin , Einsle Oliver
Published: August 2023

Mono- and multiheme cytochromes c are post-translationally matured by the covalent attachment of heme. For this, Escherichia coli employs the most complex type of maturation machineries, the Ccm-system (for cytochrome cmaturation). It consists of two membrane protein complexes, one of which shuttles heme across the membrane to a mobile chaperone that then delivers the cofactor to the second complex, an apoprotein:heme lyase, for covalent attachment. Here we report cryo-electron microscopic structures of the heme translocation complex CcmABCD from E. coli, alone and bound to the heme chaperone CcmE. CcmABCD forms a heterooctameric complex centered around the ABC transporter CcmAB that does not by itself transport heme. Our data suggest that the complex flops a heme group from the inner to the outer leaflet at its CcmBC interfaces, driven by ATP hydrolysis at CcmA. A conserved heme-handling motif (WxWD) at the periplasmic side of CcmC rotates the heme by 90° for covalent attachment to the heme chaperone CcmE that we find interacting exclusively with the CcmB subunit.
PINK1 and Parkin regulate IP3R-mediated ER calcium release
Authors: Ham Su Jin , Yoo Heesuk , Woo Daihn , Lee Da Hyun , Park Kyu-Sang , Chung Jongkyeong
Published: August 2023

Although defects in intracellular calcium homeostasis are known to play a role in the pathogenesis of Parkinson’s disease (PD), the underlying molecular mechanisms remain unclear. Here, we show that loss of PTEN-induced kinase 1 (PINK1) and Parkin leads to dysregulation of inositol 1,4,5-trisphosphate receptor (IP3R) activity, robustly increasing ER calcium release. In addition, we identify that CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) functions downstream of Parkin to directly control IP3R. Both genetic and pharmacologic suppression of CISD1 and its Drosophila homolog CISD (also known as Dosmit) restore the increased ER calcium release in PINK1 and Parkin null mammalian cells and flies, respectively, demonstrating the evolutionarily conserved regulatory mechanism of intracellular calcium homeostasis by the PINK1-Parkin pathway. More importantly, suppression of CISD in PINK1 and Parkin null flies rescues PD-related phenotypes including defective locomotor activity and dopaminergic neuronal degeneration. Based on these data, we propose that the regulation of ER calcium release by PINK1 and Parkin through CISD1 and IP3R is a feasible target for treating PD pathogenesis.
Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans
Authors: Hendrix Sebastian , Kingma Jenina , Ottenhoff Roelof , Valiloo Masoud , Svecla Monika , Zijlstra Lobke F. , Sachdev Vinay , Kovac Kristina , Levels Johannes H. M. , Jongejan Aldo , de Boer Jan F. , Kuipers Folkert , Rimbert Antoine , Norata Giuseppe D. , Loregger Anke , Zelcer Noam
Published: August 2023

The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. We recently identified SPRING as a post-transcriptional regulator of SREBP activation. Constitutive or inducible global ablation of Spring in mice is not tolerated, and we therefore develop liver-specific Spring knockout mice (LKO). Transcriptomics and proteomics analysis reveal attenuated SREBP signaling in livers and hepatocytes of LKO mice. Total plasma cholesterol is reduced in male and female LKO mice in both the low-density lipoprotein and high-density lipoprotein fractions, while triglycerides are unaffected. Loss of Spring decreases hepatic cholesterol and triglyceride content due to diminished biosynthesis, which coincides with reduced very-low-density lipoprotein secretion. Accordingly, LKO mice are protected from fructose diet-induced hepatosteatosis. In humans, we find common genetic SPRING variants that associate with circulating high-density lipoprotein cholesterol and ApoA1 levels. This study positions SPRING as a core component of hepatic SREBP signaling and systemic lipid metabolism in mice and humans.
A frontal transcallosal inhibition loop mediates interhemispheric balance in visuospatial processing
Authors: Wang Yanjie , Chen Zhaonan , Ma Guofen , Wang Lizhao , Liu Yanmei , Qin Meiling , Fei Xiang , Wu Yifan , Xu Min , Zhang Siyu
Published: August 2023

Interhemispheric communication through the corpus callosum is required for both sensory and cognitive processes. Impaired transcallosal inhibition causing interhemispheric imbalance is believed to underlie visuospatial bias after frontoparietal cortical damage, but the synaptic circuits involved remain largely unknown. Here, we show that lesions in the mouse anterior cingulate area (ACA) cause severe visuospatial bias mediated by a transcallosal inhibition loop. In a visual-change-detection task, ACA callosal-projection neurons (CPNs) were more active with contralateral visual field changes than with ipsilateral changes. Unilateral CPN inactivation impaired contralateral change detection but improved ipsilateral detection by altering interhemispheric interaction through callosal projections. CPNs strongly activated contralateral parvalbumin-positive (PV+) neurons, and callosal-input-driven PV+ neurons preferentially inhibited ipsilateral CPNs, thus mediating transcallosal inhibition. Unilateral PV+ neuron activation caused a similar behavioral bias to contralateral CPN activation and ipsilateral CPN inactivation, and bilateral PV+ neuron activation eliminated this bias. Notably, restoring interhemispheric balance by activating contralesional PV+ neurons significantly improved contralesional detection in ACA-lesioned animals. Thus, a frontal transcallosal inhibition loop comprising CPNs and callosal-input-driven PV+ neurons mediates interhemispheric balance in visuospatial processing, and enhancing contralesional transcallosal inhibition restores interhemispheric balance while also reversing lesion-induced bias.
Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins
Authors: Liu Wenzhe , Chen Limin , Yin Dongbao , Yang Zhiheng , Feng Jianfei , Sun Qi , Lai Luhua , Guo Xuefeng
Published: August 2023

Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. We use the device to study c-Myc interaction with Max and/or small molecule inhibitors. We observe the self-folding/unfolding process of c-Myc and reveal its interaction mechanism with Max and inhibitors through ultrasensitive real-time monitoring. We capture a relatively stable encounter intermediate ensemble of c-Myc during its transition from the unbound state to the fully folded state. The c-Myc/Max and c-Myc/inhibitor dissociation constants derived are consistent with other ensemble experiments. These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery.
Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)
Authors: Shariff Muhammed , Dobariya Aksharkumar , Albaghdadi Obada , Awkal Jacob , Moussa Hadi , Reyes Gabriel , Syed Mansur , Hart Robert , Longfellow Cameron , Douglass Debra , El Ahmadieh Tarek Y. , Good Levi B. , Jakkamsetti Vikram , Kathote Gauri , Angulo Gus , Ma Qian , Brown Ronnie , Dunbar Misha , Shelton John M. , Evers Bret M. , Patnaik Sourav , Hoffmann Ulrike , Hackmann Amy E. , Mickey Bruce , Peltz Matthias , Jessen Michael E. , Pascual Juan M.
Published: August 2023

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) was delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.
The impact of time length to Boolean remission for tight disease activity control after acquisition in rheumatoid arthritis patients
Authors: Yoshii Ichiro , Chijiwa Tatsumi , Sawada Naoya
Published: August 2023

Clinical importance of time length from initiation under treat-to-target (T2T) strategy to acquisition of clinical remission (TL) in treating patients with rheumatoid arthritis (RA) on disease activity control, daily activities, and quality of life maintenance was investigated. In patients who achieved Boolean remission once or more, relationship between TL and patients’ background data at initiation, and relationship between TL and mean simplified disease activity score (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) score, pain score with visual analog scale (PS-VAS), Sharp/van der Heijde Score (SHS) and quality of life score (QOLS) at the first remission and thereafter were evaluated statistically. Patients were divided into two groups whether TL was within 6 months or longer (G ≤ 6 and G > 6). Change of the parameters and Boolean remission rate (BRR) after the first remission between the two groups were compared statistically. In 465 patients, TL correlated significantly with the SDAI score, the HAQ score, PS-VAS, SHS, and the QOLS after the remission. The SDAI score and the BRR after the remission were significantly better in the G ≤ 6 than in the G > 6. TL is an important key to guarantee good and stable clinical course in treating under T2T.
Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers
Authors: Chen Chao , Liu Haozhen , Li Yanlin , Liu Jixian
Published: August 2023

The proteins encoded by the excision repair cross-complementing (ERCC) family are pivotal in DNA damage repair and maintaining genome stability. However, the precise role of the ERCC family in tumor prognosis and the effectiveness of immune checkpoint inhibitors (ICI) therapy remain uncertain. This study aimed to explore the connection between ERCC mutations and prognosis as well as the response to ICI. We observed that patients with ERCC mutations exhibited enhanced progression-free survival (PFS) and overall survival (OS) in two independent pan-cancer cohorts. Furthermore, this mutant subgroup showed higher tumor mutation burden (TMB) compared to the wild-type subgroup. Notably, ERCC mutations were associated with better OS (HR 0.54, 95% CI 0.42–0.70; P < 0.001) in pan-cancer patients who underwent ICI therapy (N = 1661). These findings were validated in a separate cohort, where patients in the ERCC mutant subgroup demonstrated improved clinical outcomes (HR 0.56, 95% CI 0.37–0.84; P = 0.03) and higher response rates (51.9% vs. 26.8%) than the wild-type subgroup. Further analysis revealed that patients with ERCC mutations displayed elevated tumor neoantigen burden (TNB) levels and increased infiltration of immune-response cells. Our study suggests that ERCC mutations are linked to enhanced immunogenicity and improved ICI efficacy, thus potentially serving as a biomarker for ICI therapy.
Bio-organic fertilizers promote yield, chemical composition, and antioxidant and antimicrobial activities of essential oil in fennel (Foeniculum vulgare) seeds
Authors: Abdelbaky Ahmed S. , Mohamed Abir M. H. A. , Abd El-Mageed Taia A. , Rady Mostafa M. , Alshehri Fatma , El-Saadony Mohamed T. , AbuQamar Synan F. , El-Tarabily Khaled A. , Al-Elwany Omar A. A.
Published: August 2023

The aromatic fennel plant (Foeniculum vulgareMiller) is cultivated worldwide due to its high nutritional and medicinal values. The aim of the current study was to determine the effect of the application of bio-organic fertilization (BOF), farmyard manure (FM) or poultry manure (PM), either individually or combined withLactobacillus plantarum(LP) and/orLactococcus lactis(LL) on the yield, chemical composition, and antioxidative and antimicrobial activities of fennel seed essential oil (FSEO). In general, PM + LP + LL and FM + LP + LL showed the best results compared to any of the applications of BOF. Among the seventeen identified FSEO components,trans-anethole (78.90 and 91.4%), fenchone (3.35 and 10.10%), limonene (2.94 and 8.62%), and estragole (0.50 and 4.29%) were highly abundant in PM + LP + LL and FM + LP + LL, respectively. In addition, PM + LP + LL and FM + LP + LL exhibited the lowest half-maximal inhibitory concentration (IC50) values of 8.11 and 9.01 μg mL−1, respectively, compared tol-ascorbic acid (IC50 = 35.90 μg mL−1). We also observed a significant (P > 0.05) difference in the free radical scavenging activity of FSEO in the triple treatments. The in vitro study using FSEO obtained from PM + LP + LL or FM + LP + LL showed the largest inhibition zones against all tested Gram positive and Gram negative bacterial strains as well as pathogenic fungi. This suggests that the triple application has suppressive effects against a wide range of foodborne bacterial and fungal pathogens. This study provides the first in-depth analysis of Egyptian fennel seeds processed utilizing BOF treatments, yielding high-quality FSEO that could be used in industrial applications.
Phase angle is related to physical function and quality of life in preoperative patients with lumbar spinal stenosis
Authors: Otsubo Ryota , Hashida Ryuki , Murotani Kenta , Iwanaga Sohei , Hirota Keisuke , Koya Shunji , Tsukada Yuya , Ogata Yuta , Yokosuka Kimiaki , Yoshida Tatsuhiro , Nakae Ichiro , Fudo Takuma , Morito Shinji , Shimazaki Takahiro , Yamada Kei , Sato Kimiaki , Matsuse Hiroo , Shiba Naoto , Hiraoka Koji
Published: August 2023

Lumbar spinal stenosis (LSS) can interfere with daily life and quality of life (QOL). Evaluating physical function and QOL and helping patients to improve is the focus of rehabilitation. Phase angle (PhA) assessment is widely used to measure body composition and is considered an indicator of physical function and QOL. This study investigated the relationship between PhA and physical function, physical activity, and QOL in patients with LSS. PhA, handgrip strength, walking speed, Timed Up and Go test (TUG), Life Space Assessment (LSA), Prognostic Nutritional Index (PNI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and EQ-5D were assessed and statistically analyzed. The study included 133 patients with LSS. Multiple regression analysis of PhA adjusted for age, sex, and body mass index (Model 1) and for Model 1 + PNI (Model 2) showed significant correlations (P < 0.05) with handgrip strength, walking speed, TUG, and LSA. Regarding QOL, PhA was significantly correlated (P < 0.05) with lumbar function in JOABPEQ. PhA was associated with physical function and QOL in patients with LSS and might be a new clinical indicator in this population.
Genetic architecture of tuber-bound free amino acids in potato and effect of growing environment on the amino acid content
Authors: Pandey Jeewan , Thompson Dalton , Joshi Madhumita , Scheuring Douglas C. , Koym Jeffrey W. , Joshi Vijay , Vales M. Isabel
Published: August 2023

Free amino acids in potato tubers contribute to their nutritional value and processing quality. Exploring the natural variation in their accumulation in tubers across diverse genetic backgrounds is critical to potato breeding programs aiming to enhance or partition their distribution effectively. This study assessed variation in the tuber-bound free amino acids in a diversity panel of tetraploid potato clones developed and maintained by the Texas A&M Potato Breeding Program to explore their genetic basis and to obtain genomic-estimated breeding values for applied breeding purposes. Free amino acids content was evaluated in tubers of 217 tetraploid potato clones collected from Dalhart, Texas in 2019 and 2020, and Springlake, Texas in 2020. Most tuber amino acids were not affected by growing location, except histidine and proline, which were significantly lower (− 59.0%) and higher (+ 129.0%), respectively, at Springlake, Texas (a location that regularly suffers from abiotic stresses, mainly high-temperature stress). Single nucleotide polymorphism markers were used for genome-wide association studies and genomic selection of clones based on amino acid content. Most amino acids showed significant variations among potato clones and moderate to high heritabilities. Principal component analysis separated fresh from processing potato market classes based on amino acids distribution patterns. Genome-wide association studies discovered 33 QTL associated with 13 free amino acids. Genomic-estimated breeding values were calculated and are recommended for practical potato breeding applications to select parents and advance clones with the desired free amino acid content.
A highly efficient scheme for library preparation from single-stranded DNA
Authors: Miura Fumihito , Kanzawa-Kiriyama Hideaki , Hisano Osamu , Miura Miki , Shibata Yukiko , Adachi Noboru , Kakuda Tsuneo , Shinoda Ken-ichi , Ito Takashi
Published: August 2023

Although methods for sequencing library preparation from double-stranded DNA are well established, those from single-stranded DNA (ssDNA) have not been well studied. Further, the existing methods have limitations in efficiency and yield. Therefore, we developed a highly efficient procedure for sequencing library preparation from ssDNA. In this method, the first adaptor tagging of ssDNA is performed using terminal deoxyribonucleotidyl transferase (TdT)-assisted adenylate connector-mediated ssDNA (TACS) ligation, which we reported recently. After complementary strand synthesis using the adaptor-tagged ssDNA, second adaptor tagging via Vaccinia virus topoisomerase I (VTopoI or TOPO)-based adaptor ligation is performed. With additional steps for degradation, repression, and removal of the adaptor dimer, the proposed TACS-TOPO scheme realizes adaptor dimer-free sequencing library preparation from ssDNA samples of 24 pg. The TACS-TOPO scheme was successfully applied to cell-free DNA analysis with amplification-free library preparation from 50 µL of human serum. A modified TACS-TOPO scheme was also applied to DNA extracted from ancient human bones, bringing two to eight times more library yields than those using a conventional library preparation protocol. The procedures for preparing VTopoI and its complex with a double-stranded oligonucleotide adaptor are also described. Overall, the proposed TACS-TOPO scheme can facilitate practical and sensitive sequencing analysis of ssDNA.
Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients
Authors: Dwivedi Nehanjali , Shukla Nidhi , Prathima K. M. , Das Manjula , Dhar Sujan K.
Published: August 2023

Cancer-associated fibroblasts (CAFs), a prominent component of the tumor microenvironment, play an important role in tumor development, invasion, and drug resistance. The expression of distinct “CAF-markers” which separates CAFs from normal fibroblasts and epithelial cells, have traditionally been used to identify them. These commonly used CAF-markers have been reported to differ greatly across different CAF subpopulations, even within a cancer type. Using an unbiased -omic approach from public data and in-house RNAseq data from patient derived novel CAF cells, TIMP-1, SPARC, COL1A2, COL3A1 and COL1A1 were identified as potential CAF-markers by differential gene expression analysis using publicly available single cell sequencing data and in-house RNAseq data to distinguish CAF populations from tumor epithelia and normal oral fibroblasts. Experimental validation using qPCR and immunofluorescence revealed CAF-specific higher expression of TIMP-1 and COL1A2 as compared to other markers in 5 novel CAF cells, derived from patients of diverse gender, habits and different locations of head and neck squamous cell carcinoma (HNSC). Upon immunohistochemical (IHC) analysis of FFPE blocks however, COL1A2 showed better differential staining between tumor epithelia and tumor stroma. Similar data science driven approach utilizing single cell sequencing and RNAseq data from stabilized CAFs can be employed to identify CAF-markers in various cancers.
Photonic helicoid-like surface states in chiral metamaterials
Authors: Chern Ruey-Lin
Published: August 2023

We investigate the photonic topological phases in chiral metamaterials characterized by the magnetoelectric tensors with diagonal chirality components. The underlying medium is considered a photonic analogue of the topological semimetal featured with a Weyl cone and a cylindrical surface in the frequency-wave vector space. As the ’spin’-degenerate condition is satisfied, the photonic system can be rearranged as two hybrid modes that are completely decoupled. By introducing the pseudospin states as the basis for the hybrid modes, the photonic system is described by two subsystems in the form of spin-orbit Hamiltonians of spin 1, which result in nonzero spin Chern numbers that determine the topological properties. Surface modes at the interface between vacuum and the chiral metamaterial exist in their common gap in the wave vector space, which are analytically formulated by algebraic equations. In particular, the surface modes form a pair of spiral surface sheets wrapping around the Weyl cone, resembling the helicoid surface states that occur in topological semimetals. At the Weyl frequency, the surface modes contain two Fermi arc-like states that concatenate to yield a straight line segment.