bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico identification of tetraspanins in monopisthocotylean (Platyhelminthes: Monogenea) parasites of fish
Authors: Caña-Bozada V. , Morales-Serna F.N. , Huerta-Ocampo J.Á. , Avalos-Soriano A.
Published: March 2022

Tetraspanins are a superfamily of transmembrane proteins that in flatworms have structural roles in the development, maturation or stability of the tegument. Several tetraspanins are considered as potential candidates for vaccines or drugs against helminths. Monopisthocotylean monogeneans are ectoparasites of fish that are health hazards for farmed fish. The aim of this study was to identify in silico putative tetraspanins in the genomic datasets of four monopisthocotylean species. The analysis predicted and classified 40 tetraspanins in Rhabdosynochus viridisi, 39 in Scutogyrus longicornis, 22 in Gyrodactylus salaris and 13 in Neobenedenia melleni, belonging to 13 orthologous groups. The high divergence of tetraspanins made it difficult to annotate their function. However, a conserved group was identified in different metazoan taxa. According to this study, metazoan tetraspanins can be divided into 17 monophyletic groups. Of the 114 monogenean tetraspanins, only seven were phylogenetically close to tetraspanins from non-platyhelminth metazoans, which suggests that this group of proteins shows rapid sequence divergence. The similarity of the monopisthocotylean tetraspanins was highest with trematodes, followed by cestodes and then free-living platyhelminths. In total, 27 monopisthocotylean-specific and 34 flatworm-specific tetraspanins were identified. Four monogenean tetraspanins were orthologous to TSP-1, which is a candidate for the development of vaccines and a potential pharmacological target in trematodes and cestodes. Although studies of tetraspanins in parasitic flatworms are scarce, this is an interesting group of proteins for the development of new methods to control monogeneans.
Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes
Authors: Chang Chiao-Erh , Wang Jui , Lin Yi-Ting , Chiu Chih-Chiang , Hsieh Ming-Hsien , Huang Ming-Chyi , Lu Mong-Liang , Chen Hsi-Chung , Chen Wei J. , Kuo Po-Hsiu
Published: March 2022

Backgrounds

A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups.

Methods

This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups.

Results

The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups.

Conclusions

Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.
Evil is not evidence
Authors: Almeida Mike
Published: March 2022

The article aims to show that, if S5 is the logic of metaphysical necessity, then no state of affairs in any possible world constitutes any non-trivial evidence for or against the existence of the traditional God. There might well be states of affairs in some worlds describing extraordinary goods and extraordinary evils, but it is false that these states of affairs constitute any (non-trivial) evidence for or against the existence of God. The epistemological and metaphysical consequences for philosophical theology of assuming that S4 or Kσρ is the logic of metaphysical necessity are equally untenable. S4 guarantees that God does not exist if there is the slightest evidence against the existence of God. And Kσρ guarantees that God might survive the loss or acquisition of any essential property at all.
Goodness, gratitude and divine freedom
Authors: Duby Steven J.
Published: March 2022

This essay considers the goodness of God and the psalmists’ gratitude toward God in connection with divine aseity and divine freedom. The plenitude of God's goodness entails that he is fully sufficient and actualised in himself. The psalmists’ gratitude toward God implies that he acts in freedom when he communicates his goodness to creatures. The essay then explores how contemplating this teaching in the Psalter can help us to articulate in a broader dogmatic scope the coherence of God's pure actuality, freedom and constancy.
Toxic entanglements: Multispecies politics, white phosphorus, and the Iraq War in Alaska
Authors: Leep Matthew
Published: March 2022

This article explores avian experiences with toxic war processes that unfold across space and time. Joining together three evolving areas of interest in global politics – ontologies of war, interspecies relations, and sensory politics – the article develops a view of war that centres ongoing war processes that affect more-than-human life in and outside of international warzones. Advancing a multispecies form of inquiry attentive to local voices, including Upper Cook Inlet Tribes, the article examines how interspecies relations emerge in national security debates about long-lasting ecological costs of war. Specifically, it offers an analysis of US Department of Defense hearings surrounding the controversy over reopening Eagle River Flats – an Alaskan estuary that had been polluted with white phosphorus munitions – for weapons testing and training during the Iraq War. The article also considers the experiences of two migratory avian communities (northern pintails and tundra swans) with toxic white phosphorus pollution, illustrating more-than-human sensory perspectives on the space and time of war processes. These conceptual and empirical moves reposition national security concerns about wartime risk into a much broader post-anthropocentric perspective.
Machines and music: instrumental contributions to bluegrass
Authors: Newton Neil
Published: March 2022

In the performance of bluegrass fiddle tunes, each repetition of the tune is generally played on a different instrument. I argue that the degree to which the instrument can influence the motivic material in improvised passages is beyond idiomaticism – where phrases might suit one instrument more than another – to the point where melodic pitch collections are shaped by the instrument itself. By combining post-human philosophies with music theories that emphasise instrument–player relationships, this essay shows how non-humans exercise agency in bluegrass improvisation. The resultant instrument-influenced passages contrast with each other, as each is played on a different instrument. This can help to signify formal structure within a performance, while the recurrence of particular instrument-influenced elements can be seen as a genre marker in bluegrass.
Transitioning from conversation analysis to mixed methods
Authors: Seedhouse Paul
Published: March 2022

This reflective piece tells the story of how I started out doing Conversation Analysis (CA) and have been transitioning into doing mixed methods for some years now. My basic argument is that language learning talk is too complex a phenomenon to analyse using a single methodology. Specifically, it is extremely difficult to isolate from the interaction concrete evidence of the learning of specific individual items in terms of change of cognitive state. This is owing to the singular complexity of language learning, which adds an extra level of complexity to language learning talk, hence supercomplexity. Of course, the counter-argument to this would be that CA as a methodology is designed to reveal the complexity and fluidity of spoken interaction. The complex organisation of ordinary conversation (Sacks et al., 1974) and of varieties of institutional interaction (Drew & Heritage, 1992) have been very well established for a very long time. CA has been extremely successful and popular as a methodology for the analysis of spoken interaction in a huge range of settings. There have been many CA studies of language learning talk over the last few decades, including my own. So why do I now feel that it cannot portray the full complexity of language learning talk on its own? There is an idiosyncratic problem with language learning talk, namely that it has an additional level of complexity superimposed on top of the regular problems of analysing spoken interaction. This is because language is the object as well as the vehicle of language learning talk.
Post-operative vomiting and enhanced recovery after congenital cardiac surgery
Authors: Parra M. Fernanda , Brown Morgan L. , Staffa Steven J. , Nathan Meena , Roy Nathalie
Published: March 2022

Background:

Post-operative nausea and vomiting is frequent after congenital cardiac surgery.

Aims:

We sought to determine factors associated to severe post-operative vomiting after congenital cardiac surgery and the effect on post-operative outcomes.

Methods:

Patients > 30 days of age who underwent elective cardiac surgical repair as part of an enhanced recovery after congenital cardiac surgery programme were retrospectively reviewed. Patient characteristics and perioperative factors were compared by univariate analysis for patients with severe post-operative vomiting, defined as three events or more, and for patients with no-or-mild post-operative vomiting. All variables with a p-value < 0.1 were included in a multivariable model, and major post-operative outcomes were compared using regression analysis.

Results:

From 1 October, 2018 to 30 September, 2019, 430 consecutive patients were included. The median age was 4.8 years (interquartile range 1.2–12.6). Twenty-one per cent of patients (91/430) experienced severe post-operative vomiting. Total intraoperative opioids > 5.0 mg/kg of oral morphine equivalent (adjusted odds ratio 1.72) and post-operative inotropes infusion(s) (adjusted odds ratio 1.64) were identified as independent predictors of severe post-operative vomiting after surgery. Patients suffering from severe post-operative vomiting had increased pulmonary complications (adjusted odds ratio 5.18) and longer post-operative hospitalisation (adjusted coefficient, 0.89).

Conclusions:

Greater cumulative intraoperative opioids are associated with severe post-operative vomiting after congenital cardiac surgery. Multimodal pain strategies targeting the reduction of intraoperative opioids should be considered during congenital cardiac surgery to enhance recovery after surgery.
Unattended distributional training can shift phoneme boundaries
Authors: Chládková Kateřina , Boersma Paul , Escudero Paola
Published: March 2022

Listeners are sensitive to speech sounds’ probability distributions. Distributional training (DT) studies with adults typically involve conscious activation of phoneme labels. We show that distributional exposure can shift existing phoneme boundaries (Spanish /e/–/i/) pre-attentively. Using a DT paradigm involving two bimodal distributions we assessed listener's neural discrimination across three sounds, showing pre-to-post-test improvement for the two adjacent sounds that fell into different clusters of the trained distribution than for those that fell into one cluster. Upon unattended exposure to an intricate stimulus set, listeners thus relocate native phoneme boundaries. We assessed whether the paradigm also works for category creation (Spanish establishing a duration contrast), where it has methodological advantages over the usual unimodal-versus-bimodal paradigm. DT yielded a greater effect for the /e/–/i/ boundary shift than for duration contrast creation. It seems that second-language phoneme contrasts similar to native ones might be easier to acquire than new contrasts.
Surviving Mars: new insights into the persistence of facultative anaerobic microbes from analogue sites
Authors: Beblo-Vranesevic Kristina , Piepjohn Johanna , Antunes Andre , Rettberg Petra
Published: March 2022

Mars analogue environments are some of the most extreme locations on Earth. Their unique combination of multiples extremes (e.g. high salinity, anoxia and low nutrient availability) make them valuable sources for finding new polyextremophilic microbes, and for exploring the limits of life. Mars, especially at its surface, is still considered to be very hostile to life but it probably possesses geological subsurface niches where the occurrence of (polyextremophilic) life is conceivable. Despite their well-recognized relevance, current knowledge on the capability of (facultative) anaerobic microbes to withstand extraterrestrial/Martian conditions, either as single strains or in communities, is still very sparse. Therefore, space experiments simulating the Martian environmental conditions by using space as a tool for astrobiological research are needed to substantiate the hypotheses of habitability of Mars. Addressing this knowledge gap is one of the main goals of the project MEXEM (Mars EXposed Extremophiles Mixture), where selected model organisms will be subjected to space for a period of 3 months. These experiments will take place on the Exobiology facility (currently under development and implementation), located outside the International Space Station. Such space experiments require a series of preliminary tests and ground data collection for the selected microbial strains. Here, we report on the survivability ofSalinisphaera shabanensisandButtiauxellasp. MASE-IM-9 after exposure to Mars-relevant stress factors (such as desiccation and ultraviolet (UV) radiation under anoxia). Both organisms showed survival after anoxic desiccation for up to 3 months but this could be further extended (nearly doubled) by adding artificial Mars regolith (MGS-1S; 0.5% wt/v) and sucrose (0.1 M). Survival after desiccation was also observed when both organisms were mixed before treatment. Mixing also positively influenced survival after exposure to polychromatic Mars-like UV radiation (200–400 nm) up to 12 kJ m−2, both in suspension and in a desiccated form.
THE LOCAL-ORBIFOLD CORRESPONDENCE FOR SIMPLE NORMAL CROSSING PAIRS
Authors: Battistella Luca , Nabijou Navid , Tseng Hsian-Hua , You Fenglong
Published: March 2022

For X a smooth projective variety and
$D=D_1+\dotsb +D_n$
a simple normal crossing divisor, we establish a precise cycle-level correspondence between the genus
$0$
local Gromov–Witten theory of the bundle
$\oplus _{i=1}^n \mathcal {O}_X(-D_i)$
and the maximal contact Gromov–Witten theory of the multiroot stack
$X_{D,\vec r}$
. The proof is an implementation of the rank-reduction strategy. We use this point of view to clarify the relationship between logarithmic and orbifold invariants.
The Story behind the First Automatic Atomic Force Microscope
Authors: Yoo Ryan YK
Published: March 2022

Over the past three decades, atomic force microscopy (AFM) has undergone a series of design changes to attain a flat XY scan and stable non-contact mode in ambient atmosphere. AFM has evolved into an ideal method for non-destructive scanning of samples with longer probe tip life, high accuracy, repeatability, and automation. Together with self-optimizing algorithms for scan parameters in the non-contact mode, AFM can become as widely adopted as other microscopies such as optical or scanning electron microscopy (SEM). Even full automation of AFM probe tip exchange is now possible with probe type recognition software and laser beam alignment on the cantilever and position-sensitive photo diode (PSPD). By separating the optics stage from the Z stage, an AFM system can be made with low mechanical noise and improved optical vision.
Shame
Authors: Théberge David , Gamache Dominick
Published: March 2022

Abstract. While shame is sometimes discussed as a key element at the core of personality pathologies, its relationship with pathological personality traits is still understudied. Previous research suggested that shame is a common subjective experience in patients with borderline and narcissistic personality traits. However, little is known about how borderline and narcissistic traits are associated with specific areas of shame in community samples. The present study aims to investigate these associations, using a dual strategy, that is, both at “variable-level” using correlational analyses and at “person-level” using a cluster-analytic strategy with borderline and narcissistic (grandiose and vulnerable) personality traits as clustering variables. A total of 254 French-Canadian adult participants were recruited to complete an online battery of self-report questionnaires. Correlational analyses revealed that borderline-related traits and narcissistic vulnerability showed some significant and meaningful differences pertaining to Behavioral shame while sharing a similar pattern of associations with Characterological and Bodily shame. Alternatively, shame does not appear to be a strong correlate of narcissistic grandiosity, although some significant – and somewhat unexpected – positive associations between the two were found. Cluster analysis yielded four groups based on their levels of pathological traits; the groups showed indiscriminate associations with different shame areas, suggesting that the association between shame and pathological traits is more global and less area specific.
Ablation Rates of Organic Compounds in Cosmic Dust and Resulting Changes in Mechanical Properties During Atmospheric Entry
Authors: Bones David L. , Carrillo Sánchez Juan Diego , Connell Simon D. A. , Kulak Alexander N. , Mann Graham W. , Plane John M. C.
Published: March 2022

A new experimental system is described for studying the pyrolysis of the refractory organic constituents in cosmic dust during atmospheric entry. The pyrolysis kinetics of meteoritic fragments (CM2 and CV3 carbonaceous chondrites, radius = 36–100 μm) were measured by mass spectrometric detection of CO2 and SO2 at temperatures between 625 and 1300 K, with most carbon being lost between 700 and 800 K. The complex time‐resolved kinetic behavior is consistent with two organic components—one significantly more refractory than the other, which probably correspond to the insoluble and soluble organic fractions, respectively. The measured temperature‐dependent pyrolysis rates were then incorporated into the Leeds Chemical Ablation Model, which demonstrates that organic pyrolysis should be detectable using a high performance/large aperture radar. Atomic force microscopy was used to show that although the residual meteoritic particles became more brittle after organic pyrolysis, they also became slightly harder, withstanding stresses that are at least three orders of magnitude higher than would be encountered during atmospheric entry. This suggests that most cosmic dust particles (radius <100 μm) will not fragment during entry into the atmosphere as a result of organic pyrolysis, although a subset of slow‐moving, low density particles mostly from Jupiter‐family comets could fragment.
Electron Densities in the Ionosphere of Mars: Comparison of MAVEN/ROSE and MAVEN/LPW Measurements
Authors: Felici M. , Withers P. , Vogt M. F. , Hensley K. G. , Andersson L.
Published: March 2022

Several different instrument types have been widely used to measure the density of plasma in solar system ionospheres. However, limitations in spatial and temporal coverage have prevented efforts to directly compare electron density measured by different kinds of instrument in order to assess whether systematic errors exist in such measurements. Here, we exploit the excellent observational coverage provided at Mars by the MAVEN spacecraft to compare numerous electron density measurements from two instruments, the Radio Occultation Science Experiment (ROSE, a remote sensing investigation) and Langmuir Probe and Waves (LPW, an in situ instrument). For dusk local times, we find that systematic contrasts between ROSE and LPW electron density measurements are less than 4 × 103 cm−3. As this limit is only modestly greater than the intrinsic measurement uncertainty on ROSE electron density observations, we conclude that any systematic error present in either data set is smaller than the instrumental accuracies. Differences are larger, between 8 × 103 and 1.2 × 104 cm−3, at dawn local times. From the differences, ratios, and percentage difference between the ROSE and LPW densities, we postulate that electron densities are more variable in the dawn ionosphere than in the dusk ionosphere.
Monotonic Increase of Extreme Precipitation Intensity With Temperature When Controlled for Saturation Deficit
Authors: Wang Guiling , Sun Xiaoming
Published: March 2022

Past studies based on univariate scaling analyses at the weather time scale documented a negative scaling of extreme precipitation intensity (EPI), which prevents EPI extrapolation from past climate. Here we present a bivariate scaling analysis and show that, contrary to the univariate scaling results, EPI monotonically increases with temperature and shows no negative scaling when controlled for saturation deficit. The observed EPI‐temperature relationship in saturated atmosphere is surprisingly similar among different regions and closely follows the Clausius‐Clapeyron scaling; climate models produce greater regional dependence of the scaling relationship with a wide range of scaling rate. For extratropical regions, the model‐simulated EPI‐temperature relationship under saturation shows a past‐to‐future continuity, which could potentially support extrapolation to a warmer climate. The scaling at saturation bridges the EPI‐temperature relationship between weather and climate time scales and may enable potential prediction of future precipitation extremes via extrapolation from past observations.
Serendipitous Internal Wave Signals in Deep Argo Data
Authors: Johnson Gregory C. , Whalen Caitlin B. , Purkey Sarah G. , Zilberman Nathalie
Published: March 2022

Serendipitous measurements of deep internal wave signatures are evident in oscillatory variations around the background descent rates reported by one model of Deep Argo float. For the 10,045 profiles analyzed here, the average root‐mean‐square of vertical velocity variances, , from 1,000 m to the seafloor, is 0.0045 m s−1, with a 5%–95% range of 0.0028–0.0067 m s−1. Dominant vertical wavelengths, λz, estimated from the integrals of lagged autocorrelation sequences have an average value of 757 m, with a 5%–95% range of 493–1,108 m. Both and λz exhibit regional variations among and within some deep ocean basins, with generally larger and shorter λz in regions of rougher bathymetry or stronger deep currents. These correlations are both expected, since larger and shorter λz should be found near internal wave generation regions.
Weight-based discrimination in financial reward and punishment decision making: causal evidence using a novel experimental paradigm
Authors: Jones Andrew , Hardman Charlotte A. , Devlin Niamh , Pennington Charlotte R. , Robinson Eric
Published: March 2022

Background/Objectives

Cross-sectional research has demonstrated weight-related stigma and discrimination, however experimental research providing causal evidence of financial-based weight discrimination is lacking. The aim of these preregistered experiments was to examine whether a novel paradigm in which participants attributed financial rewards and punishments could be used to detect weight bias.

Subjects/Methods

One-hundred and twenty-one individuals participated in experiment 1 and one-hundred and sixty-six individuals participated in experiment 2. Both studies were conducted online, and participants were provided with biographies of hypothetical individuals in which weight-status was manipulated (normal weight vs. overweight/obesity) before being asked to provide rewards and punishments on their cognitive performance. In experiment 1 (within-participants design) participants observed one individual they believed to be normal weight and one individual they believed to be overweight/have obesity. In experiment 2 (between-participants design) participants observed one individual whilst also being provided with information about food addiction (Food addiction is real + individual with overweight/obesity vs. food addiction is a myth + individual with overweight/obesity vs control + individual with normal weight).

Results

In experiment 1, participants punished individuals who were described as having overweight/obesity to a greater extent to individuals who were normal weight (Hedge’sg = −0.21 [95% CI: −0.02 to −0.41],p = 0.026), but there was no effect on rewards. They were also less likely to recommend individuals with overweight/obesity to pass the tasks (X2(1) = 10.05,p = 0.002). In experiment 2, participants rewarded individuals whom they believed were overweight/obese to a lesser extent than normal-weight individuals(g = 0.49 [95% CI: 0.16 to 0.83]. There was no effect on punishment, nor any impact of information regarding food addiction as real vs a myth.

Conclusion

Using a novel discrimination task, these two experiments demonstrate causal evidence of weight-based discrimination in financial decision making.
Trefoil factor 3 promotes pancreatic carcinoma progression via WNT pathway activation mediated by enhanced WNT ligand expression
Authors: Cheng Feifei , Wang Xuejuan , Chiou Yi-Shiou , He Chuyu , Guo Hui , Tan Yan Qin , Basappa Basappa , Zhu Tao , Pandey Vijay , Lobie Peter E.
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related mortality with a dismal prognosis that has changed little over the past few decades. Further understanding of the molecular pathology of PDAC progression is urgently required in order to improve the prognosis of patients with PDAC. Herein, it was observed that trefoil factor 3 (TFF3) expression was elevated in PDAC, and was positively correlated with a worse overall patient survival outcome. Forced expression of TFF3 promoted oncogenic functions of PDAC cells in vitro including cell proliferation, survival, foci formation, cancer stem cell-like behavior and invasion, ex vivo colony growth in 3D-Matrigel, and xenograft growth in vivo. Depletion or pharmacological inhibition of TFF3 inhibited these same processes. RNA-Seq analysis and subsequent mechanistic analyses demonstrated that TFF3 increased the expression of various WNT ligands to mediate WNT pathway activation required for TFF3-stimulated PDAC progression. Combined pharmacological inhibition of TFF3 and WNT signaling significantly attenuated PDAC xenograft growth and potentiated the therapeutic efficacy of gemcitabine in both ex vivo and in vivo models. Hence, a mechanistic basis for combined inhibition of pathways enhancing PDAC progression is provided and suggests that inhibition of TFF3 may assist to ameliorate outcomes in PDAC.
RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma
Authors: Qin Yuan , Sun Wei , Wang Zhihong , Dong Wenwu , He Liang , Zhang Ting , Lv Chengzhou , Zhang Hao
Published: March 2022

Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.
CAMTA1–PPP3CA–NFATc4 multi-protein complex mediates the resistance of colorectal cancer to oxaliplatin
Authors: Pan Ruijun , Zhang Zhou , Jia Hongtao , Ma Junjun , Wu Chao , Xue Pei , Cai Wei , Zhang Xiaoping , Sun Jing
Published: March 2022

Colorectal cancer is a major contributor to the worldwide prevalence of cancer-related deaths. Metastasis and chemoresistance are the two main causes for colorectal cancer treatment failure, and thus, high mortality. Calmodulin-binding transcription activator 1 (CAMTA1) is involved in tumor growth and development, but its mechanisms of action in the development of colorectal cancer and chemoresistance are poorly understood. Here, we report that Camta1 is a tumor suppressor. Immunohistochemical staining and western blotting analyses of normal and colorectal cancer tissues showed a significantly low expression of Camta1 expression in colorectal cancer tissues, when compared to adjacent normal tissues. In functional in vitro experiments, we observed that Camta1 overexpression significantly decreased the proliferation and invasion capacity of SW620 and SW480 cells, whereas Camta1 knockdown displayed a significant increase in the proliferative and invasive ability of these cells. Subsequently, we examined the effects of Camta1 overexpression and knockdown on the resistance of colorectal cancer cells to oxaliplatin, a common chemotherapeutic drug. Interestingly, the sensitivity of Camta1-overexpressed cells to oxaliplatin was increased, whereas that of Camta1-silenced cells to the same chemotherapeutic drug was decreased. Furthermore, Camta1 knockdown upregulated nuclear factor of activated T cells, cytoplasmic 4 (Nfatc4) mRNA, and protein levels in colorectal cancer cells and downregulated the phosphorylated NFATc4 level. By contrast, Nfatc4 knockdown reversed the resistance of colorectal cancer cells to oxaliplatin caused by Camta1 knockdown. In addition, we show that protein phosphatase 3 catalytic subunit alpha (PPP3CA) is essential for the expression and phosphorylation of NFATc4 caused by Camta1 knockdown, as well as the proliferation, invasion, and chemoresistance of colorectal cancer cells. We show that PPP3CA and CAMTA1 competitively bind to NFATc4, and Camta1 knockdown promotes the dephosphorylation of PPP3CA and suppresses the phosphorylation of NFATc4. To verify the role of CAMTA1 in oxaliplatin resistance in colorectal cancer, we established a xenograft mouse model and show agreement between in vitro and in vivo results.
Ubiquitin conjugating enzyme E2 C (UBE2C) may play a dual role involved in the progression of thyroid carcinoma
Authors: Xiang Cheng , Yan Hai-chao
Published: March 2022

The present study aimed to explore the role of ubiquitin-conjugating enzyme E2 C (UBE2C) in the progress of thyroid carcinoma (THCA). We firstly explored the prognostic impact and expression level of UBE2C in THCA. Then, we performed the UBE2C knockdown and evaluated the effects on the proliferation, cell cycle distribution, apoptosis, migration, and invasion of THCA cells, as well as resistance to sorafenib. Finally, we predicted the possible pathways and explored the correlation between UBE2C with immune infiltrates. The results showed that high expression of UBE2C independently predicted a shorter disease-free survival time of THCA patients. And UBE2C also presented a better prognostic performance on the survival probability of patients. Expression analysis showed that UBE2C was statistically upregulated in THCA tissue compared with normal tissue. After UBE2C knockdown, the proliferation of THCA cells was inhibited and apoptosis was increased. These results indicated that UBE2C acted as an oncogene in THCA. However, the migration and invasion of THCA cells with UBE2C knockdown were enhanced, and the expressions of migration-related proteins were upregulated. In addition, UBE2C knockdown increased the resistance of THCA cells to sorafenib. These results implied the potential of UBE2C as a suppressor gene in THCA. The pathway analysis further predicted that metabolism-related pathways were activated in the UBE2C low expression class, and cell growth and immune-related pathways were focused on the UBE2C high expression class. Finally, we observed a significant positive relationship between UBE2C and several immune infiltrates in THCA. It followed that UBE2C high expression might play a vital role in THCA to some extent. This study revealed that UBE2C participated in the progression of THCA and may play the dual role of both oncogene and tumor suppressor gene. The detailed mechanism needed to be further investigated.
Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment
Authors: Rapata Micah E. J. , Zhang Jie , Cunningham William J. , Hadden Peter W. , Patel Dipika V. , McGhee Charles N. J.
Published: March 2022

Background/Objectives

Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes.

Subjects/Methods

Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival.

Results

Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Māori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%.

Conclusion

In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.
Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria
Authors: Yang Huan , Sibilla Caroline , Liu Raymond , Yun Jina , Hay Bruce A. , Blackstone Craig , Chan David C. , Harvey Robert J. , Guo Ming
Published: March 2022

Mitochondrial fission is critically important for controlling mitochondrial morphology, function, quality and transport. Drp1 is the master regulator driving mitochondrial fission, but exactly how Drp1 is regulated remains unclear. Here, we identifiedDrosophilaClueless and its mammalian orthologue CLUH as key regulators of Drp1. As with loss ofdrp1, depletion ofcluelessorCLUHresults in mitochondrial elongation, while as withdrp1overexpression,cluelessorCLUHoverexpression leads to mitochondrial fragmentation. Importantly,drp1overexpression rescues adult lethality, tissue disintegration and mitochondrial defects ofcluelessnull mutants inDrosophila. Mechanistically, Clueless and CLUH promote recruitment of Drp1 to mitochondria from the cytosol. This involves CLUH binding to mRNAs encoding Drp1 receptors MiD49 and Mff, and regulation of their translation. Our findings identify a crucial role of Clueless and CLUH in controlling mitochondrial fission through regulation of Drp1.
Biosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups
Authors: Liu Yongfei , Wang Wei , Zeng An-Ping
Published: March 2022

Diols encompass important bulk and fine chemicals for the chemical, pharmaceutical and cosmetic industries. During the past decades, biological production of C3-C5 diols from renewable feedstocks has received great interest. Here, we elaborate a general principle for effectively synthesizing structurally diverse diols by expanding amino acid metabolism. Specifically, we propose to combine oxidative and reductive formations of hydroxyl groups from amino acids in a thermodynamically favorable order of four reactions catalyzed by amino acid hydroxylase, L-amino acid deaminase, α-keto acid decarboxylase and aldehyde reductase consecutively. The oxidative formation of hydroxyl group from an alkyl group is energetically more attractive than the reductive pathway, which is exclusively used in the synthetic pathways of diols reported so far. We demonstrate this general route for microbial production of branched-chain diols in E. coli. Ten C3-C5 diols are synthesized. Six of them, namely isopentyldiol (IPDO), 2-methyl-1,3-butanediol (2-M-1,3-BDO), 2-methyl-1,4-butanediol (2-M-1,4-BDO), 2-methyl-1,3-propanediol (MPO), 2-ethyl-1,3-propanediol (2-E-1,3-PDO), 1,4-pentanediol (1,4-PTD), have not been biologically synthesized before. This work opens up opportunities for synthesizing structurally diverse diols and triols, especially by genome mining, rational design or directed evolution of proper enzymes.
Global impacts of future urban expansion on terrestrial vertebrate diversity
Authors: Li Guangdong , Fang Chuanglin , Li Yingjie , Wang Zhenbo , Sun Siao , He Sanwei , Qi Wei , Bao Chao , Ma Haitao , Fan Yupeng , Feng Yuxue , Liu Xiaoping
Published: March 2022

Rapid urban expansion has profound impacts on global biodiversity through habitat conversion, degradation, fragmentation, and species extinction. However, how future urban expansion will affect global biodiversity needs to be better understood. We contribute to filling this knowledge gap by combining spatially explicit projections of urban expansion under shared socioeconomic pathways (SSPs) with datasets on habitat and terrestrial biodiversity (amphibians, mammals, and birds). Overall, future urban expansion will lead to 11–33 million hectares of natural habitat loss by 2100 under the SSP scenarios and will disproportionately cause large natural habitat fragmentation. The urban expansion within the current key biodiversity priority areas is projected to be higher (e.g., 37–44% higher in the WWF’s Global 200) than the global average. Moreover, the urban land conversion will reduce local within-site species richness by 34% and species abundance by 52% per 1 km grid cell, and 7–9 species may be lost per 10 km cell. Our study suggests an urgent need to develop a sustainable urban development pathway to balance urban expansion and biodiversity conservation.
Scale-invariant machine-learning model accelerates the discovery of quaternary chalcogenides with ultralow lattice thermal conductivity
Authors: Pal Koushik , Park Cheol Woo , Xia Yi , Shen Jiahong , Wolverton Chris
Published: March 2022

We design an advanced machine-learning (ML) model based on crystal graph convolutional neural network that is insensitive to volumes (i.e., scale) of the input crystal structures to discover novel quaternary chalcogenides, AMM′Q3 (A/M/M' = alkali, alkaline earth, post-transition metals, lanthanides, and Q = chalcogens). These compounds are shown to possess ultralow lattice thermal conductivity (κl), a desired requirement for thermal-barrier coatings and thermoelectrics. Upon screening the thermodynamic stability of ~1 million compounds using the ML model iteratively and performing density-functional theory (DFT) calculations for a small fraction of compounds, we discover 99 compounds that are validated to be stable in DFT. Taking several DFT-stable compounds, we calculate their κl using Peierls–Boltzmann transport equation, which reveals ultralow κl (<2 Wm−1K−1 at room temperature) due to their soft elasticity and strong phonon anharmonicity. Our work demonstrates the high efficiency of scale-invariant ML model in predicting novel compounds and presents experimental-research opportunities with these new compounds.
Flexible Miniaturized Sensor Technologies for Long-Term Physiological Monitoring
Authors: He Rongyan , Liu Hao , Niu Yan , Zhang Huiqing , Genin Guy M. , Xu Feng
Published: March 2022

Physiological monitoring can provide detailed information about health conditions, and therefore presents great potentials for personalized healthcare. Flexible miniaturized sensors (FMS) for physiological monitoring have garnered significant attention because of their wide applications in collecting health-related information, evaluating and managing the state of human wellness in long term. In this review, we focus on the time scale of human physiological monitoring, the needs and advances in miniaturized technologies for long-term monitoring in typical applications. We also discuss the rational sample sources of FMS to select proper strategies for specific monitoring cases. Further, existing challenges and promising prospects are also presented.
In-operando analysis of the corrosion patterns and rates under magnetic fields using metallic film
Authors: Mitre Cirlei Igreja Nascimento , Tosin Giancarlo , Colnago Luiz Alberto
Published: March 2022

Magnets, or electromagnets, are common components in everyday appliances and are widely used in medicine, industries, transportation, and electrical power systems. It is known that the magnetic field (B) can mitigate or aggravate metallic corrosion; however, this apparent contradictory effect is still not fully understood. In this study, we demonstrate a simple method to monitor in-operando the effect of permanent magnets (B) on corrosion processes using metallic film (copper clad laminate), FeCl3 solution as corrosive medium, and digital camera to record the experiments. The results show that homogeneous and inhomogeneous B decrease or increase the corrosion rate, respectively. The homogeneous and inhomogeneous B also shows different corrosion patterns and induces rotation of the corrosive medium indicating the presence of the Lorentz force. The procedure proposed can also be applied to other metals and corrosive media providing valuable information on the corrosion process in the presence of B in several environmental conditions.
A critical review of marine biofilms on metallic materials
Authors: Tuck B. , Watkin E. , Somers A. , Machuca L. L.
Published: March 2022

The formation of multi-species biofilms on marine infrastructure costs the global economy US $ billions annually, resulting in biofouling and microbiologically influenced corrosion. It is well documented that complex biofilms form on almost any submerged surface, yet there are still no truly effective and environmentally friendly treatment or prevention options available. An incomplete fundamental understanding of natural biofilm development remains a key limitation for biofilm control measures. The purpose of this review is to compile the current literature and knowledge gaps surrounding the development of multi-species biofilms in marine conditions on metals.
The potential convergence of NLRP3 inflammasome, potassium, and dopamine mechanisms in Parkinson’s disease
Authors: Pike Adrianne F. , Szabò Ildikò , Veerhuis Robert , Bubacco Luigi
Published: March 2022

The pathology of Parkinson’s disease (PD) is characterized by α-synuclein aggregation, microglia-mediated neuroinflammation, and dopaminergic neurodegeneration in the substantia nigra with collateral striatal dopamine signaling deficiency. Microglial NLRP3 inflammasome activation has been linked independently to each of these facets of PD pathology. The voltage-gated potassium channel Kv1.3, upregulated in microglia by α-synuclein and facilitating potassium efflux, has also been identified as a modulator of neuroinflammation and neurodegeneration in models of PD. Evidence increasingly suggests that microglial Kv1.3 is mechanistically coupled with NLRP3 inflammasome activation, which is contingent on potassium efflux. Potassium conductance also influences dopamine release from midbrain dopaminergic neurons. Dopamine, in turn, has been shown to inhibit NLRP3 inflammasome activation in microglia. In this review, we provide a literature framework for a hypothesis in which Kv1.3 activity-induced NLRP3 inflammasome activation, evoked by stimuli such as α-synuclein, could lead to microglia utilizing dopamine from adjacent dopaminergic neurons to counteract this process and fend off an activated state. If this is the case, a sufficient dopamine supply would ensure that microglia remain under control, but as dopamine is gradually siphoned from the neurons by microglial demand, NLRP3 inflammasome activation and Kv1.3 activity would progressively intensify to promote each of the three major facets of PD pathology: α-synuclein aggregation, microglia-mediated neuroinflammation, and dopaminergic neurodegeneration. Risk factors overlapping to varying degrees to render brain regions susceptible to such a mechanism would include a high density of microglia, an initially sufficient supply of dopamine, and poor insulation of the dopaminergic neurons by myelin.
Gastrointestinal involvement in Parkinson’s disease: pathophysiology, diagnosis, and management
Authors: Warnecke T. , Schäfer K-H. , Claus I. , Del Tredici K. , Jost W. H.
Published: March 2022

Growing evidence suggests an increasing significance for the extent of gastrointestinal tract (GIT) dysfunction in Parkinson’s disease (PD). Most patients suffer from GIT symptoms, including dysphagia, sialorrhea, bloating, nausea, vomiting, gastroparesis, and constipation during the disease course. The underlying pathomechanisms of this α-synucleinopathy play an important role in disease development and progression, i.e., early accumulation of Lewy pathology in the enteric and central nervous systems is implicated in pharyngeal discoordination, esophageal and gastric motility/peristalsis impairment, chronic pain, altered intestinal permeability and autonomic dysfunction of the colon, with subsequent constipation. Severe complications, including malnutrition, dehydration, insufficient drug effects, aspiration pneumonia, intestinal obstruction, and megacolon, frequently result in hospitalization. Sophisticated diagnostic tools are now available that permit more detailed examination of specific GIT impairment patterns. Furthermore, novel treatment approaches have been evaluated, although high-level evidence trials are often missing. Finally, the burgeoning literature devoted to the GIT microbiome reveals its importance for neurologists. We review current knowledge about GIT pathoanatomy, pathophysiology, diagnosis, and treatment in PD and provide recommendations for management in daily practice.