bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible mediators of metabolic endotoxemia in women with obesity and women with obesity-diabetes in The Gambia
Authors: Jobe Modou , Agbla Schadrac C. , Todorcevic Marijana , Darboe Bakary , Danso Ebrima , de Barros Jean-Paul Pais , Lagrost Laurent , Karpe Fredrik , Prentice Andrew M.
Published: August 2022

Aims/hypothesis

Translocation of bacterial debris from the gut causes metabolic endotoxemia (ME) that results in insulin resistance, and may be on the causal pathway to obesity-related type 2 diabetes. To guide interventions against ME we tested two hypothesised mechanisms for lipopolysaccharide (LPS) ingress: a leaky gut and chylomicron-associated transfer following a high-fat meal.

Methods

In lean women (n = 48; fat mass index (FMI) 9.6 kg/m2), women with obesity (n = 62; FMI 23.6 kg/m2) and women with obesity-diabetes (n = 38; FMI 24.9 kg/m2) we used the lactulose-mannitol dual-sugar permeability test (LM ratio) to assess gut integrity. Markers of ME (LPS, EndoCAb IgG and IgM, IL-6, CD14 and lipoprotein binding protein) were assessed at baseline, 2 h and 5 h after a standardised 49 g fat-containing mixed meal. mRNA expression of markers of inflammation, macrophage activation and lipid metabolism were measured in peri-umbilical adipose tissue (AT) biopsies.

Results

The LM ratio did not differ between groups. LPS levels were 57% higher in the obesity-diabetes group (P < 0.001), but, contrary to the chylomicron transfer hypothesis, levels significantly declined following the high-fat challenge. EndoCAb IgM was markedly lower in women with obesity and women with obesity-diabetes. mRNA levels of inflammatory markers in adipose tissue were consistent with the prior concept that fat soluble LPS in AT attracts and activates macrophages.

Conclusions/interpretation

Raised levels of LPS and IL-6 in women with obesity-diabetes and evidence of macrophage activation in adipose tissue support the concept of metabolic endotoxemia-mediated inflammation, but we found no evidence for abnormal gut permeability or chylomicron-associated post-prandial translocation of LPS. Instead, the markedly lower EndoCAb IgM levels indicate a failure in sequestration and detoxification.
Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts
Authors: Silventoinen Karri , Li Weilong , Jelenkovic Aline , Sund Reijo , Yokoyama Yoshie , Aaltonen Sari , Piirtola Maarit , Sugawara Masumi , Tanaka Mami , Matsumoto Satoko , Baker Laura A. , Tuvblad Catherine , Tynelius Per , Rasmussen Finn , Craig Jeffrey M. , Saffery Richard , Willemsen Gonneke , Bartels Meike , van Beijsterveldt Catharina E. M. , Martin Nicholas G. , Medland Sarah E. , Montgomery Grant W. , Lichtenstein Paul , Krueger Robert F. , McGue Matt , Pahlen Shandell , Christensen Kaare , Skytthe Axel , Kyvik Kirsten O. , Saudino Kimberly J. , Dubois Lise , Boivin Michel , Brendgen Mara , Dionne Ginette , Vitaro Frank , Ullemar Vilhelmina , Almqvist Catarina , Magnusson Patrik K. E. , Corley Robin P. , Huibregtse Brooke M. , Knafo-Noam Ariel , Mankuta David , Abramson Lior , Haworth Claire M. A. , Plomin Robert , Bjerregaard-Andersen Morten , Beck-Nielsen Henning , Sodemann Morten , Duncan Glen E. , Buchwald Dedra , Burt S. Alexandra , Klump Kelly L. , Llewellyn Clare H. , Fisher Abigail , Boomsma Dorret I. , Sørensen Thorkild I. A. , Kaprio Jaakko
Published: August 2022

Background

Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height.

Methods

We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age.

Results

The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood.

Conclusions

Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.
Effects of mild obesity on outcomes in Japanese patients with COVID-19: a nationwide consortium to investigate COVID-19 host genetics
Authors: Lee Ho , Chubachi Shotaro , Namkoong Ho , Tanaka Hiromu , Otake Shiro , Nakagawara Kensuke , Morita Atsuho , Fukushima Takahiro , Watase Mayuko , Kusumoto Tatsuya , Masaki Katsunori , Kamata Hirofumi , Ishii Makoto , Hasegawa Naoki , Harada Norihiro , Ueda Tetsuya , Ueda Soichiro , Ishiguro Takashi , Arimura Ken , Saito Fukuki , Yoshiyama Takashi , Nakano Yasushi , Mutoh Yoshikazu , Suzuki Yusuke , Murakami Koji , Okada Yukinori , Koike Ryuji , Kitagawa Yuko , Kimura Akinori , Imoto Seiya , Miyano Satoru , Ogawa Seishi , Kanai Takanori , Fukunaga Koichi ,   The Japan COVID-19 Task Force
Published: August 2022

Background

Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population.

Methods

From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died.

Results

Class 1 obesity (25.0 ≤ BMI < 30.0 kg/m2), class 2 obesity (30.0 ≤ BMI < 35.0 kg/m2), and class 3 or 4 obesity (BMI ≥ 35 kg/m2) were present in 29%, 8%, and 3% of the cases, respectively. Multiple logistic regression analysis with known risk factors for critical illness indicated that class 2 obesity was an independent risk factor for oxygenation (adjusted odds ratio, 4.75) and critical cases (adjusted odds ratio, 1.81). Class 1 obesity and class 3 or 4 obesity were independent risk factors for oxygen administration (adjusted odds ratios 2.01 and 3.12, respectively), but not for critical cases. However, no differences in the mortality rates were observed between the BMI classes (P = 0.5104).

Conclusion

Obesity is a risk factor for respiratory failure in Japanese patients with COVID-19, regardless of the degree of obesity. However, it may not cause severe COVID-19 in a dose–response relationship with BMI. COVID-19 patients with mild obesity may benefit from aggressive intensive care.
Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants
Authors: Turunen Jenni , Tejesvi Mysore V. , Suokas Marko , Virtanen Nikke , Paalanne Niko , Kaisanlahti Anna , Reunanen Justus , Tapiainen Terhi
Published: August 2022

Background

Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods.

Methods

We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics.

Results

We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant.

Conclusions

Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods.

Impact

We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants.

This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods.

This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.
shRNA‑mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8
Authors: Liu Ruijun , Liu Ruili , Guo Zhiyi , Ren Jianghao , Huang Jia , Luo Qingquan , Tan Qiang
Published: August 2022

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.
An open-label pilot study of recombinant granulocyte-colony stimulating factor in Friedreich’s ataxia
Authors: Kemp Kevin C. , Georgievskaya Anastasia , Hares Kelly , Redondo Juliana , Bailey Steven , Rice Claire M. , Scolding Neil J. , Metcalfe Chris , Wilkins Alastair
Published: August 2022

Friedreich’s ataxia (FA) is an inherited progressive neurodegenerative disease for which there is no proven disease-modifying treatment. Here we perform an open‐label, pilot study of recombinant human granulocyte-colony stimulating factor (G-CSF) administration in seven people with FA (EudraCT: 2017-003084-34); each participant receiving a single course of G-CSF (Lenograstim; 1.28 million units per kg per day for 5 days). The primary outcome is peripheral blood mononuclear cell frataxin levels over a 19-day period. The secondary outcomes include safety, haematopoietic stem cell (HSC) mobilisation, antioxidant levels and mitochondrial enzyme activity. The trial meets pre-specified endpoints. We show that administration of G-CSF to people with FA is safe. Mobilisation of HSCs in response to G-CSF is comparable to that of healthy individuals. Notably, sustained increases in cellular frataxin concentrations and raised PGC-1α and Nrf2 expression are detected. Our findings show potential for G-CSF therapy to have a clinical impact in people with FA.
Erasure conversion for fault-tolerant quantum computing in alkaline earth Rydberg atom arrays
Authors: Wu Yue , Kolkowitz Shimon , Puri Shruti , Thompson Jeff D.
Published: August 2022

Executing quantum algorithms on error-corrected logical qubits is a critical step for scalable quantum computing, but the requisite numbers of qubits and physical error rates are demanding for current experimental hardware. Recently, the development of error correcting codes tailored to particular physical noise models has helped relax these requirements. In this work, we propose a qubit encoding and gate protocol for171Yb neutral atom qubits that converts the dominant physical errors into erasures, that is, errors in known locations. The key idea is to encode qubits in a metastable electronic level, such that gate errors predominantly result in transitions to disjoint subspaces whose populations can be continuously monitored via fluorescence. We estimate that 98% of errors can be converted into erasures. We quantify the benefit of this approach via circuit-level simulations of the surface code, finding a threshold increase from 0.937% to 4.15%. We also observe a larger code distance near the threshold, leading to a faster decrease in the logical error rate for the same number of physical qubits, which is important for near-term implementations. Erasure conversion should benefit any error correcting code, and may also be applied to design new gates and encodings in other qubit platforms.
Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses
Authors: Pardi Norbert , Carreño Juan Manuel , O’Dell George , Tan Jessica , Bajusz Csaba , Muramatsu Hiromi , Rijnink Willemijn , Strohmeier Shirin , Loganathan Madhumathi , Bielak Dominika , Sung Molly M. H. , Tam Ying K. , Krammer Florian , McMahon Meagan
Published: August 2022

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.
Identification of a non-axisymmetric mode in laboratory experiments searching for standard magnetorotational instability
Authors: Wang Yin , Gilson Erik P. , Ebrahimi Fatima , Goodman Jeremy , Caspary Kyle J. , Winarto Himawan W. , Ji Hantao
Published: August 2022

The standard magnetorotational instability (SMRI) is a promising mechanism for turbulence and rapid accretion in astrophysical disks. It is a magnetohydrodynamic (MHD) instability that destabilizes otherwise hydrodynamically stable disk flow. Due to its microscopic nature at astronomical distances and stringent requirements in laboratory experiments, SMRI has remained unconfirmed since its proposal, despite its astrophysical importance. Here we report a nonaxisymmetric MHD instability in a modified Taylor-Couette experiment. To search for SMRI, a uniform magnetic field is imposed along the rotation axis of a swirling liquid-metal flow. The instability initially grows exponentially, becoming prominent only for sufficient flow shear and moderate magnetic field. These conditions for instability are qualitatively consistent with SMRI, but at magnetic Reynolds numbers below the predictions of linear analyses with periodic axial boundaries. Three-dimensional numerical simulations, however, reproduce the observed instability, indicating that it grows linearly from the primary axisymmetric flow modified by the applied magnetic field.
Repeated genetic adaptation to altitude in two tropical butterflies
Authors: Montejo-Kovacevich Gabriela , Meier Joana I. , Bacquet Caroline N. , Warren Ian A. , Chan Yingguang Frank , Kucka Marek , Salazar Camilo , Rueda-M Nicol , Montgomery Stephen H. , McMillan W. Owen , Kozak Krzysztof M. , Nadeau Nicola J. , Martin Simon H. , Jiggins Chris D.
Published: August 2022

Repeated evolution can provide insight into the mechanisms that facilitate adaptation to novel or changing environments. Here we study adaptation to altitude in two tropical butterflies, Heliconius erato and H. melpomene, which have repeatedly and independently adapted to montane habitats on either side of the Andes. We sequenced 518 whole genomes from altitudinal transects and found many regions differentiated between highland (~ 1200 m) and lowland (~ 200 m) populations. We show repeated genetic differentiation across replicate populations within species, including allopatric comparisons. In contrast, there is little molecular parallelism between the two species. By sampling five close relatives, we find that a large proportion of divergent regions identified within species have arisen from standing variation and putative adaptive introgression from high-altitude specialist species. Taken together our study supports a role for both standing genetic variation and gene flow from independently adapted species in promoting parallel local adaptation to the environment.
Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health
Authors: Gadd Danni A. , Hillary Robert F. , McCartney Daniel L. , Shi Liu , Stolicyn Aleks , Robertson Neil A. , Walker Rosie M. , McGeachan Robert I. , Campbell Archie , Xueyi Shen , Barbu Miruna C. , Green Claire , Morris Stewart W. , Harris Mathew A. , Backhouse Ellen V. , Wardlaw Joanna M. , Steele J. Douglas , Oyarzún Diego A. , Muniz-Terrera Graciela , Ritchie Craig , Nevado-Holgado Alejo , Chandra Tamir , Hayward Caroline , Evans Kathryn L. , Porteous David J. , Cox Simon R. , Whalley Heather C. , McIntosh Andrew M. , Marioni Riccardo E.
Published: August 2022

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening
Authors: Ioannou Marianna , Hoving Dennis , Aramburu Iker Valle , Temkin Mia I. , De Vasconcelos Nathalia M. , Tsourouktsoglou Theodora-Dorita , Wang Qian , Boeing Stefan , Goldstone Robert , Vernardis Spyros , Demichev Vadim , Ralser Markus , David Sascha , Stahl Klaus , Bode Christian , Papayannopoulos Venizelos
Published: August 2022

The mechanisms linking systemic infection to hyperinflammation and immune dysfunction in sepsis are poorly understood. Extracellular histones promote sepsis pathology, but their source and mechanism of action remain unclear. Here, we show that by controlling fungi and bacteria captured by splenic macrophages, neutrophil-derived myeloperoxidase attenuates sepsis by suppressing histone release. In systemic candidiasis, microbial capture via the phagocytic receptor SIGNR1 neutralizes myeloperoxidase by facilitating marginal zone infiltration and T cell death-dependent histone release. Histones and hyphae induce cytokines in adjacent CD169 macrophages including G-CSF that selectively depletes mature Ly6Ghigh neutrophils by shortening their lifespan in favour of immature Ly6Glow neutrophils with a defective oxidative burst. In sepsis patient plasma, these mediators shorten mature neutrophil lifespan and correlate with neutrophil mortality markers. Consequently, high G-CSF levels and neutrophil lifespan shortening activity are associated with sepsis patient mortality. Hence, by exploiting phagocytic receptors, pathogens degrade innate and adaptive immunity through the detrimental impact of downstream effectors on neutrophil lifespan.
Ultra-flat and long-lived plasmons in a strongly correlated oxide
Authors: Gao Han , Ding Chao , Son Jaeseok , Zhu Yangyu , Wang Mingzheng , Yu Zhi Gen , Chen Jianing , Wang Le , Chambers Scott A. , Noh Tae Won , Zhao Mingwen , Li Yangyang
Published: August 2022

Plasmons in strongly correlated systems are attracting considerable attention due to their unconventional behavior caused by electronic correlation effects. Recently, flat plasmons with nearly dispersionless frequency-wave vector relations have drawn significant interest because of their intriguing physical origin and promising applications. However, these flat plasmons exist primarily in low-dimensional materials with limited wave vector magnitudes (q < ~0.7 Å−1). Here, we show that long-lived flat plasmons can propagate up to ~1.2 Å−1 in α-Ti2O3, a strongly correlated three-dimensional Mott-insulator, with an ultra-small energy fluctuation (<40 meV). The strong correlation effect renormalizes the electronic bands near Fermi level with a small bandwidth, which is responsible for the flat plasmons in α-Ti2O3. Moreover, these flat plasmons are not affected by Landau damping over a wide range of wave vectors (q < ~1.2 Å−1) due to symmetry constrains on the electron wavefunctions. Our work provides a strategy for exploring flat plasmons in strongly correlated systems, which in turn may give rise to novel plasmonic devices in which flat and long-lived plasmons are desirable.
MYC sensitises cells to apoptosis by driving energetic demand
Authors: Edwards-Hicks Joy , Su Huizhong , Mangolini Maurizio , Yoneten Kubra K. , Wills Jimi , Rodriguez-Blanco Giovanny , Young Christine , Cho Kevin , Barker Heather , Muir Morwenna , Guerrieri Ania Naila , Li Xue-Feng , White Rachel , Manasterski Piotr , Mandrou Elena , Wills Karen , Chen Jingyu , Abraham Emily , Sateri Kianoosh , Qian Bin-Zhi , Bankhead Peter , Arends Mark , Gammoh Noor , von Kriegsheim Alex , Patti Gary J. , Sims Andrew H. , Acosta Juan Carlos , Brunton Valerie , Kranc Kamil R. , Christophorou Maria , Pearce Erika L. , Ringshausen Ingo , Finch Andrew J.
Published: August 2022

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.
Shielded soft force sensors
Authors: Aksoy Bekir , Hao Yufei , Grasso Giulio , Digumarti Krishna Manaswi , Cacucciolo Vito , Shea Herbert
Published: August 2022

Force and strain sensors made of soft materials enable robots to interact intelligently with their surroundings. Capacitive sensing is widely adopted thanks to its low power consumption, fast response, and facile fabrication. Capacitive sensors are, however, susceptible to electromagnetic interference and proximity effects and thus require electrical shielding. Shielding has not been previously implemented in soft capacitive sensors due to the parasitic capacitance between the shield and sensing electrodes, which changes when the sensor is deformed. We address this crucial challenge by patterning the central sensing elastomer layer to control its compressibility. One design uses an ultrasoft silicone foam, and the other includes microchannels filled with liquid metal and air. The force resolution is sub-mN both in normal and shear directions, yet the sensor withstands large forces (>20 N), demonstrating a wide dynamic range. Performance is unaffected by nearby high DC and AC electric fields and even electric sparks.
Designing against phase and property heterogeneities in additively manufactured titanium alloys
Authors: Zhang Jingqi , Liu Yingang , Sha Gang , Jin Shenbao , Hou Ziyong , Bayat Mohamad , Yang Nan , Tan Qiyang , Yin Yu , Liu Shiyang , Hattel Jesper Henri , Dargusch Matthew , Huang Xiaoxu , Zhang Ming-Xing
Published: August 2022

Additive manufacturing (AM) creates digitally designed parts by successive addition of material. However, owing to intrinsic thermal cycling, metallic parts produced by AM almost inevitably suffer from spatially dependent heterogeneities in phases and mechanical properties, which may cause unpredictable service failures. Here, we demonstrate a synergistic alloy design approach to overcome this issue in titanium alloys manufactured by laser powder bed fusion. The key to our approach is in-situ alloying of Ti−6Al−4V (in weight per cent) with combined additions of pure titanium powders and iron oxide (Fe2O3) nanoparticles. This not only enables in-situ elimination of phase heterogeneity through diluting V concentration whilst introducing small amounts of Fe, but also compensates for the strength loss via oxygen solute strengthening. Our alloys achieve spatially uniform microstructures and mechanical properties which are superior to those of Ti−6Al−4V. This study may help to guide the design of other alloys, which not only overcomes the challenge inherent to the AM processes, but also takes advantage of the alloy design opportunities offered by AM.
Human brain structural connectivity matrices–ready for modelling
Authors: Škoch Antonín , Rehák Bučková Barbora , Mareš Jan , Tintěra Jaroslav , Sanda Pavel , Jajcay Lucia , Horáček Jiří , Španiel Filip , Hlinka Jaroslav
Published: August 2022

The human brain represents a complex computational system, the function and structure of which may be measured using various neuroimaging techniques focusing on separate properties of the brain tissue and activity. We capture the organization of white matter fibers acquired by diffusion-weighted imaging using probabilistic diffusion tractography. By segmenting the results of tractography into larger anatomical units, it is possible to draw inferences about the structural relationships between these parts of the system. This pipeline results in a structural connectivity matrix, which contains an estimate of connection strength among all regions. However, raw data processing is complex, computationally intensive, and requires expert quality control, which may be discouraging for researchers with less experience in the field. We thus provide brain structural connectivity matrices in a form ready for modelling and analysis and thus usable by a wide community of scientists. The presented dataset contains brain structural connectivity matrices together with the underlying raw diffusion and structural data, as well as basic demographic data of 88 healthy subjects.
New diterpenes from the marine sponge Spongionella sp. overcome drug resistance in prostate cancer by inhibition of P-glycoprotein
Authors: Dyshlovoy Sergey A. , Shubina Larisa K. , Makarieva Tatyana N. , Hauschild Jessica , Strewinsky Nadja , Guzii Alla G. , Menshov Alexander S. , Popov Roman S. , Grebnev Boris B. , Busenbender Tobias , Oh-Hohenhorst Su Jung , Maurer Tobias , Tilki Derya , Graefen Markus , Bokemeyer Carsten , Stonik Valentin A. , von Amsberg Gunhild
Published: August 2022

Spongian diterpenes are a group of marine natural compounds possessing various biological activities. However, their anticancer activity is still poorly studied and understood. We isolated six spongian diterpenes from the marine sponge Spongionella sp., including one new spongionellol A and five previously known molecules. The structures were elucidated using a detailed analysis MS and NMR spectra as well as by comparison with previously reported data. Two of them, namely, spongionellol A and 15,16-dideoxy-15α,17β-dihydroxy-15,17-oxidospongian-16-carboxylate-15,17-diacetate exhibited high activity and selectivity in human prostate cancer cells, including cells resistant to hormonal therapy and docetaxel. The mechanism of action has been identified as caspase-dependent apoptosis. Remarkably, both compounds were able to suppress expression of androgen receptor (AR) and AR-splice variant 7, as well as AR-dependent signaling. The isolated diterpenes effectively inhibited drug efflux mediated by multidrug-resistance protein 1 (MDR1; p-glycoprotein). Of note, a synergistic effect of the compounds with docetaxel, a substrate of p-glycoprotein, suggests resensitization of p-glycoprotein overexpressing cells to standard chemotherapy. In conclusion, the isolated spongian diterpenes possess high activity and selectivity towards prostate cancer cells combined with the ability to inhibit one of the main drug-resistance mechanism. This makes them promising candidates for combinational anticancer therapy.
Risk factors of radiographic severity of massive rotator cuff tear
Authors: Furuhata Ryogo , Matsumura Noboru , Oki Satoshi , Nishikawa Takahiro , Kimura Hiroo , Suzuki Taku , Nakamura Masaya , Iwamoto Takuji
Published: August 2022

As massive rotator cuff tears progress, various radiographic changes occur; however, the factors associated with radiographic changes remain largely unknown. This study aimed to determine the factors that affect radiographic severity in massive rotator cuff tears using multivariate analyses. We retrospectively reviewed 210 shoulders with chronic massive rotator cuff tears. The dependent variables were superior migration of the humeral head (Hamada grades 2–3), narrowing of the glenohumeral joint (grade 4), and humeral head collapse (grade 5). Baseline variables that were significant in univariate analyses were included in multivariate models. There were 91, 59, 43, and 17 shoulders classified as Hamada grades 1, 2–3, 4, and 5, respectively. Multivariate analysis showed that infraspinatus tear (P = 0.015) and long head of biceps (LHB) tendon rupture (P = 0.007) were associated with superior migration of humeral head. Superior subscapularis tear (P = 0.003) and LHB tendon rupture (P < 0.001) were associated with narrowing of glenohumeral joint. Female sex (P = 0.006) and superior subscapularis tear (P = 0.006) were associated with humeral head collapse. This study identified the rupture of infraspinatus and LHB as risk factors of superior migration of humeral head, and the rupture of subscapularis and LHB and female sex as risk factors of cuff tear arthropathy.
Cerebellar engagement in the attachment behavioral system
Authors: Picerni Eleonora , Laricchiuta D. , Piras F. , Petrosini L. , Spalletta G. , Cutuli D.
Published: August 2022

Brain structural bases of individual differences in attachment are not yet fully clarified. Given the evidence of relevant cerebellar contribution to cognitive, affective, and social functions, the present research was aimed at investigating potential associations between attachment dimensions (through the Attachment Style Questionnaire, ASQ) and cerebellar macro- and micro-structural measures (Volumetric and Diffusion Tensor Imaging data). In a sample of 79 healthy subjects, cerebellar and neocortical volumetric data were correlated with ASQ scores at the voxel level within specific Regions Of Interest. Also, correlations between ASQ scores and age, years of education, anxiety and depression levels were performed to control for the effects of sociodemographic and psychological variables on neuroimaging results. Positive associations between scores of the Preoccupation with Relationships (ASQ subscale associated to insecure/anxious attachment) and cortical volume were found in the cerebellum (right lobule VI and left Crus 2) and neocortex (right medial OrbitoFrontal Cortex, OFC) regions. Cerebellar contribution to the attachment behavioral system reflects the more general cerebellar engagement in the regulation of emotional and social behaviors. Cerebellar properties of timing, prediction, and learning well integrate with OFC processing, supporting the regulation of attachment experiences. Cerebellar areas might be rightfully included in the attachment behavioral system.
Measuring internal inequality in capsule networks for supervised anomaly detection
Authors: Kirillov Bogdan , Panov Maxim
Published: August 2022

In this paper we explore the use of income inequality metrics such as Gini or Palma coefficients as a tool to identify anomalies via capsule networks. We demonstrate how the interplay between primary and class capsules gives rise to differences in behavior regarding anomalous and normal input which can be exploited to detect anomalies. Our setup for anomaly detection requires supervision in a form of known outliers. We derive several criteria for capsule networks and apply them to a number of Computer Vision benchmark datasets (MNIST, Fashion-MNIST, Kuzushiji-MNIST and CIFAR10), as well as to the dataset of skin lesion images (HAM10000) and the dataset of CRISPR-Cas9 off-target pairs. The proposed methods outperform the competitors in the majority of considered cases.
A comprehensive list of the Bunyavirales replication promoters reveals a unique promoter structure in Nairoviridae differing from other virus families
Authors: Neriya Yutaro , Kojima Shohei , Sakiyama Arata , Kishimoto Mai , Iketani Takao , Watanabe Tadashi , Abe Yuichi , Shimoda Hiroshi , Nakagawa Keisuke , Koma Takaaki , Matsumoto Yusuke
Published: August 2022

Members of the order Bunyavirales infect a wide variety of host species, including plants, animals and humans, and pose a threat to public health. Major families in this order have tri-segmented negative-sense RNA genomes, the 5′ and 3′ ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral polymerases recognize the promoter to initiate RNA synthesis is important for understanding viral replication and pathogenesis, and developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. By using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5′ and 3′ ends of the genome that form a specific complementary strand. Among tri-segmented bunyaviruses, members of the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure differing from that of other families. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses, and the large genome architecture might confer pathogenic advantages. The promoter list provided in this report is useful for predicting the virus family-specific replication mechanisms of bunyaviruses.
Geochemical provenance of an Indo-Arabian stone anchor from Manikapatna highlights the medieval maritime trade of India
Authors: Tripati Sila , Ray Jyotiranjan S. , Behera Rudra Prasad , Babu Prakash , Mahala Milan Kumar , Kocherla Murali , Khedekar Vijay
Published: August 2022

India is one of the oldest maritime nations in the world, and the overseas contacts date back to the third millennium BCE. Besides several archaeological vestiges, numerous stone anchors of various types have been documented during maritime archaeological explorations along the Indian littoral. During a recent maritime archaeological exploration, a broken Indo-Arabian stone anchor, of the Medieval period, was discovered along the Manikapatna coast of Odisha, Indian eastern littoral. In an attempt to determine the provenance of the anchor, we carried out a detailed petrographic, geochemical (major/trace elements) and Sr–Nd isotopic investigation. The results of our study reveal that the stone of the anchor had been cut out of a geologically young, vesicular, subalkalic basalt lava flow. Source fingerprinting done using petrographic, geochemical and isotopic data, suggests that contrary to the general perception, the anchor rock did not come from any local rock formations. All data point to the most likely scenario that the anchor rock was sourced from one of the lava flows of the Deccan Traps at Palitana in the Saurashtra region of Gujarat, western India. This result confirms the existence of Medieval maritime trading between western and eastern Indian states.
The crystal structure of Cry78Aa from Bacillus thuringiensis provides insights into its insecticidal activity
Authors: Cao Beibei , Nie Yangfan , Guan Zeyuan , Chen Chuanyu , Wang Nancong , Wang Zeyu , Shu Changlong , Zhang Jie , Zhang Delin
Published: August 2022

Genetically modified plants with insecticidal proteins from Bacillus thuringiensis (Bt) have been successfully utilized to control various kinds of pests in crop production and reduce the abuse of pesticides. However, a limited number of genes are available for the protection of crops from rice planthopper. Recently, Cry78Aa protein from Bt strain C9F1 has been found to have high insecticidal activity against Laodelphax striatellus and Nilaparvata lugens. It is the first reported single-component protein in the world to combat rice planthoppers, making it very promising for use in transgenic crops. The ambiguous mechanism of Cry78Aa functions prevented further engineering or application. Here, we report the crystal structure of Cry78Aa, which consists of two domains: a C-terminal β-pore forming domain belonging to the aerolysin family and an N-terminal trefoil domain resembling the S-type ricin B lectin. Thus, Cry78Aa could represent a distinctive type of β-pore forming toxin. We also found that Cry78Aa binds carbohydrates such as galactose derivatives and is essential for insecticidal activity against Laodelphax striatellus. Our results suggest a mechanism underlying the function of Cry78Aa against rice planthoppers and pave the way to maximizing the usage of the toxin.
PYK2 senses calcium through a disordered dimerization and calmodulin-binding element
Authors: Momin Afaque A. , Mendes Tiago , Barthe Philippe , Faure Camille , Hong SeungBeom , Yu Piao , Kadaré Gress , Jaremko Mariusz , Girault Jean-Antoine , Jaremko Łukasz , Arold Stefan T.
Published: August 2022

Multidomain kinases use many ways to integrate and process diverse stimuli. Here, we investigated the mechanism by which the protein tyrosine kinase 2-beta (PYK2) functions as a sensor and effector of cellular calcium influx. We show that the linker between the PYK2 kinase and FAT domains (KFL) encompasses an unusual calmodulin (CaM) binding element. PYK2 KFL is disordered and engages CaM through an ensemble of transient binding events. Calcium increases the association by promoting structural changes in CaM that expose auxiliary interaction opportunities. KFL also forms fuzzy dimers, and dimerization is enhanced by CaM binding. As a monomer, however, KFL associates with the PYK2 FERM-kinase fragment. Thus, we identify a mechanism whereby calcium influx can promote PYK2 self-association, and hence kinase-activating trans-autophosphorylation. Collectively, our findings describe a flexible protein module that expands the paradigms for CaM binding and self-association, and their use for controlling kinase activity.
Time-sensitive prefrontal involvement in associating confidence with task performance illustrates metacognitive introspection in monkeys
Authors: Cai Yudian , Jin Zhiyong , Zhai Chenxi , Wang Huimin , Wang Jijun , Tang Yingying , Kwok Sze Chai
Published: August 2022

Metacognition refers to the ability to be aware of one’s own cognition. Ample evidence indicates that metacognition in the human primate is highly dissociable from cognition, specialized across domains, and subserved by distinct neural substrates. However, these aspects remain relatively understudied in macaque monkeys. In the present study, we investigated the functionality of macaque metacognition by combining a confidence proxy, hierarchical Bayesian meta-d′ computational modelling, and a single-pulse transcranial magnetic stimulation technique. We found that Brodmann area 46d (BA46d) played a critical role in supporting metacognition independent of task performance; we also found that the critical role of this region in meta-calculation was time-sensitive. Additionally, we report that macaque metacognition is highly domain-specific with respect to memory and perception decisions. These findings carry implications for our understanding of metacognitive introspection within the primate lineage.
Stronger responses of soil protistan communities to legacy mercury pollution than bacterial and fungal communities in agricultural systems
Authors: Du Shuai , Li Xin-Qi , Hao Xiuli , Hu Hang-Wei , Feng Jiao , Huang Qiaoyun , Liu Yu-Rong
Published: August 2022

Soil pollution is an important stressor affecting biodiversity and ecosystem functioning. However, we lack a holistic understanding of how soil microbial communities respond to heavy metal pollution in agricultural ecosystems. Here, we explored the distribution patterns and inter-kingdom interactions of entire soil microbiome (including bacteria, fungi, and protists) in 47 paired paddy and upland fields along a gradient of legacy mercury (Hg) pollution. We found that the richness and composition of protistan community had stronger responses to Hg pollution than those of bacterial and fungal communities in both paddy and upland soils. Mercury polluted soils harbored less protistan phototrophs but more protistan consumers. We further revealed that long-term Hg pollution greatly increased network complexity of protistan community than that of bacterial and fungal communities, as well as intensified the interactions between protists and the other microorganisms. Moreover, our results consistently indicated that protistan communities had stronger responses to long-term Hg pollution than bacterial and fungal communities in agricultural soils based on structural equation models and random forest analyses. Our study highlights that soil protists can be used as bioindicators of Hg pollution, with important implications for the assessment of contaminated farmlands and the sustainable management of agricultural ecosystems.
Designing photonic microparticles with droplet microfluidics
Authors: Kim Young Geon , Park Sihun , Kim Shin-Hyun
Published: August 2022

This feature article describes the recent progress and current state of the art in the microfluidic production of photonic microparticles and capsules using droplet templates.
Minor adjustments in the chemical structures of pyridine derivatives induced different co-assemblies by O–H⋯N hydrogen bonds
Authors: Lei Peng , Luo Wendi , Tu Bin , Xiao Xunwen , Fang Qiaojun , Wang Chen , Zeng Qingdao
Published: August 2022

Here, we explored the effects of chemical structures on pyridine derivatives, such as the relative positions of the nitrogen atom and the lengths of the side chain on the backbone, on acid-pyridine co-assembly structures.
Molecular dynamics simulations of the impurity effect on packing structures, local stresses, and thermodynamics of Ih silver clusters
Authors: Liu Jinhan , Zhang Lin
Published: August 2022

The doping of a Cu atom in the different cluster shells significantly affects the thermal stability and thermodynamic values of the clusters.
Investigating the abnormal conductivity behaviour of divalent cations in low dielectric constant tetraglyme-based electrolytes
Authors: Nguyen Long Hoang Bao , Picard Tanguy , Iojoiu Cristina , Alloin Fannie , Sergent Nicolas , Doublet Marie-Liesse , Filhol Jean-Sébastien
Published: August 2022

The solvation structure and ionic conductivity of Ca(TFSI)2/tetraglyme solutions were studied using a combination of experimental and theoretical approaches. A higher fraction of free ions was detected in solutions with higher molar concentrations.
Medicinal inorganic chemistry – challenges, opportunities and guidelines to develop the next generation of radioactive, photoactivated and active site inhibiting metal-based medicines
Authors: Lengacher Raphael , Marlin Axia , Śmiłowicz Dariusz , Boros Eszter
Published: August 2022

Medicinal inorganic chemistry is a burgeoning subfield of medicinal chemistry that focuses on the development of metal-based diagnostic and therapeutic agents.
Diaryl dithiocarbamates: synthesis, oxidation to thiuram disulfides, Co(iii) complexes [Co(S2CNAr2)3] and their use as single source precursors to CoS2
Authors: Sarker Jagodish C. , Nash Rosie , Boonrungsiman Suwimon , Pugh David , Hogarth Graeme
Published: August 2022

Air and moisture stable diaryl dithiocarbamate salts, Ar2NCS2Li, result from addition of CS2 to Ar2NLi. They react cleanly to afford [Co(S2CNAr2)3] which decompose in amine solutions to give CoS2.
Colon microbiota modulation by dairy-derived diet: new strategy for prevention and treatment of colorectal cancer
Authors: Gomes Sara , Teixeira-Guedes Catarina , Silva Elisabete , Baltazar Fátima , Preto Ana
Published: August 2022

The modulation of the intestinal microbiota by dairy-derived product consumption is being explored as an innovative approach to fight colorectal cancer.
Carbon-economic biosynthesis of poly-2-hydrobutanedioic acid driven by nonfermentable substrate ethanol
Authors: Wang Pan , Li Bingqin , Li Baiyue , Yang Jing , Xu Xingran , Yang Shang-Tian , Zou Xiang
Published: August 2022

Poly-2-hydrobutanedioic acid (P2HBD), produced by the yeast-like fungus Aureobasidium pullulans, is a new type of water-soluble polyhydroxy acid with potential applications in the biomaterial and biomedical fields.
High performance NiOx nanoplatelet based films by a scrape-coating method for bifunctional electrochromic and energy storage devices
Authors: Tao Xinyu , Zhang Yong , Cai Jingyi , Tan Hark Hoe , Cui Jiewu , Wang Yan , Shu Xia , Dai Zhenhong , Qin Yongqiang , Liu Jiaqin , Wu Yucheng
Published: August 2022

High performance NiOx nanoplatelet porous films were prepared and successfully applied in EC/energy storage bifunctional devices and flexible films (where the presence of Ni vacancies enhances the performance of films in Li+ electrolytes).