Miracle-dz/UniFAR-FTUs huggingface dataset:
The Immunomodulatory Potential of Copper and Silver Based Self-Assembled Metal Organic Biohybrids Nanomaterials in Cancer Theranostics

Copper high aspect ratio structures (CuHARS) and silver cystine nanoparticles (AgCysNPs) are two unique micro/nano particles under study here that show extensive anti-cancer effects on a glioma tumor cell line. These micro/nano particles have shown potent toxicity in the presence of inflammatory stimulus (combination of tumor necrosis factor, [TNF] and lipo-polysaccharide, LPS). CuHARS with a concentration of 20 μg/ml uniquely increased the catalytic generation of nitric oxide (NO), an important contributor in the immune system. This NO was generated in a cell culture tumor microenvironment (TME) in the presence of 25 µM S-nitrosothiol (cysteine-NO) and the inflammatory stimulus. CuHARS increased the NO production by 68.75% when compared to untreated glioma cells with CysNO and inflammatory stimulus. The production of NO was significantly higher under similar circumstances in the case of normal primary structural cells like brain microvascular endothelial cells (BMVECs). The production of NO by BMVECs went up by 181.25% compared to glioma cells. This significant increase in the NO concentration could have added up to tumorigenesis but the anti-cancer effect of CuHARS was prominent enough to lower down the viability of glioma cells by approximately 20% and increased the metabolism of structural cells, BMVECs by approximately 200%. The immunomodulatory effect of NO in the TME under these circumstances in the presence of the novel micro/nano material, CuHARS has risen up compared to the effect of inflammatory stimulus alone. The potency and specific nature of these materials toward tumor cells may make them suitable candidates for cancer treatment. Successive treatment of CuHARS to glioma cells also proved to be an effective approach considering the decrease in the total count of cells by 11.84 fold in case of three successive treatments compared to a single dose which only decreased the cell count by 2.45 fold showing the dose-dependent increasing toxicity toward glioma cells. AgCysNPs are another potent nanomaterial which also proved its significant toxic nature toward tumor cell lines as demonstrated here, but their immunomodulatory response is still unclear and needs to be explored further.
Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining

SUMOylation is critical for a plethora of cellular signalling pathways including the repair of DNA double-strand breaks (DSBs). If misrepaired, DSBs can lead to cancer, neurodegeneration, immunodeficiency and premature ageing. Based on systematic proteome microarray screening combined with widely applicable carbene footprinting and high-resolution structural profiling, we define two non-conventional SUMO2-binding modules on XRCC4, a DNA repair protein important for DSB repair by non-homologous end-joining (NHEJ). Mechanistically, interaction of SUMO2 with XRCC4 is incompatible with XRCC4 binding to at least two other NHEJ proteins – XLF and DNA ligase 4 (LIG4). These findings are consistent with SUMO2 interactions of XRCC4 acting as backup pathways at different stages of NHEJ, in the absence of these factors or their dysfunctioning. Such scenarios are not only relevant for carcinogenesis, but also for the design of precision anti-cancer medicines and the optimisation of CRISPR/Cas9-based gene editing. This work reveals insights into topology-specific SUMO recognition and its potential for modulating DSB repair by NHEJ. Moreover, it provides a rich resource on binary SUMO receptors that can be exploited for uncovering regulatory layers in a wide array of cellular processes.
Thermosensitive cross-linked polymer vesicles for controlled release system

Thermosensitive cross-linked polymer vesicles were formed by self-assembly of block copolymer poly(2-cinnamoylethyl methacrylate)-block-poly(N-isopropylacrylamide) (PCEMA61-b-PNIPAM22) and subsequent photo-cross-linking PCEMA shells. The ability of these polymer vesicles to load and release 4-aminopyridine (Apy), a model compound, is discussed. It is found that the polymer vesicles can load a large amount of Apy and release the compound at a tunable rate depending on the temperature. The polymer vesicles also show satisfactory reversible and reproducible thermosensitive release characteristics.
Development of Deep-Sea Anoxia in Panthalassa During the Lopingian (Late Permian): Insights From Redox-Sensitive Elements and Multivariate Analysis

The end-Permian mass extinction (EPME) was the most severe mass extinction event of the Phanerozoic, and was associated with the development of global oceanic anoxia. The intensification of ocean anoxia preceded the EPME, but the degree of intensity and timing of oceanic redox changes in the mid-Panthalassa Ocean remain debated. Here we present the results of geochemical and multivariate statistical analyses of a late Guadalupian to Lopingian (middle–late Permian) bedded chert succession from the Iwaidani section, Japan, which preserves pelagic deep-sea facies from the ocean floor to the lower flank of a mid-Panthalassan seamount. The entire section yields a low manganese-enrichment factor (MnEF <1), suggesting that suboxic conditions has appeared in the depositional environment already in the late Guadalupian. Enrichment factors of other redox-sensitive trace-elements (e.g., vanadium and uranium) and principle component analysis (PCA) of major element data show the development of suboxic to weakly anoxic conditions across the Guadalupian/Lopingian boundary. Subsequently, anoxic conditions, as inferred from enrichments in U, Mo, Ni, Cu, Zn, and Tl, were developed during the middle Lopingian. Extremely high concentrations of U and Mo (enrichment factors of ∼6 and ∼5,500, respectively) indicate that H2S-rich euxinic conditions developed during the latest Lopingian and around the time of the EPME. The cause of the shift toward more reducing conditions in the early–middle Lopingian is unknown, but PCA results suggest that the euxinic conditions occurred in association with intensified continental weathering in response to a temperature rise during the ca. 200 kyr before the EPME.
Interferon-regulated genetic programs and JAK/STAT pathway activate the intronic promoter of the short ACE2 isoform in renal proximal tubules

Recently, a short, interferon-inducible isoform of Angiotensin-Converting Enzyme 2 (ACE2), dACE2 was identified. ACE2 is a SARS-Cov-2 receptor and changes in its renal expression have been linked to several human nephropathies. These changes were never analyzed in context of dACE2, as its expression was not investigated in the kidney. We used Human Primary Proximal Tubule (HPPT) cells to show genome-wide gene expression patterns after cytokine stimulation, with emphasis on the ACE2/dACE2 locus. Putative regulatory elements controlling dACE2 expression were identified using ChIP-seq and RNA-seq. qRT-PCR differentiating between ACE2 and dACE2 revealed 300- and 600-fold upregulation of dACE2 by IFNα and IFNβ, respectively, while full length ACE2 expression was almost unchanged. JAK inhibitor ruxolitinib ablated STAT1 and dACE2 expression after interferon treatment. Finally, with RNA-seq, we identified a set of genes, largely immune-related, induced by cytokine treatment. These gene expression profiles provide new insights into cytokine response of proximal tubule cells.
Packing the Standard Genetic Code in its box: 3-dimensional late Crick wobble

Minimally-evolved codes are constructed with randomly chosen Standard Genetic Code (SGC) triplets, and completed with completely random triplet assignments. Such “genetic codes” have not evolved, but retain SGC qualities. Retained qualities are inescapable, part of the logic of code evolution. For example, sensitivity of coding to arbitrary assignments, which must be <≈ 10%, is intrinsic. Such sensitivity comes from elementary combinatorial properties of coding, and constrains any SGC evolution hypothesis. Similarly, evolution of last-evolved functions is difficult, due to late kinetic phenomena, likely common across codes. Census of minimally-evolved code assignments shows that shape and size of wobble domains controls packing into a coding table, strongly shifting accuracy of codon assignments. Access to the SGC therefore requires a plausible pathway to limited randomness, avoiding difficult completion while packing a highly ordered, degenerate code into a fixed three-dimensional space. Late Crick wobble in a 3-dimensional genetic code assembled by lateral transfer satisfies these varied, simultaneous requirements. By allowing parallel evolution of SGC domains, it can yield shortened evolution to SGC-level order, and allow the code to arise in smaller populations. It effectively yields full codes. Less obviously, it unifies well-studied sources for order in amino acid coding, including a stereochemical minority of triplet-amino acid associations. Finally, fusion of its intermediates into the definitive SGC is credible, mirroring broadly-accepted later cellular evolution.
Identification of Functional lncRNAs Associated With Ovarian Endometriosis Based on a ceRNA Network

Background Endometriosis is a common gynecological disease affecting women of reproductive age; however, the mechanisms underlying this condition are not fully clear. The aim of this study was to identify functional long non-coding RNAs (lncRNAs) associated with ovarian endometriosis for potential use as biomarkers and therapeutic targets. Methods RNA-seq profiles of paired ectopic (EC) and eutopic (EU) endometrial samples from patients with ovarian endometriosis were downloaded from the publicly available Gene Expression Omnibus (GEO) database. Bioinformatics algorithms were used to construct a network of ovarian endometriosis-related competing endogenous RNAs (ceRNAs) and to detect functional lncRNAs. Results A total of 4,213 mRNAs, 1,474 lncRNAs, and 221 miRNAs were identified as being differentially expressed between EC and EU samples, and an ovarian endometriosis-related ceRNA network was constructed through analysis of these differentially expressed RNAs. H19 and GS1-358P8.4 were identified as key ovarian endometriosis-related lncRNAs through topological feature analysis, and RP11-96D1.10 was identified using a random walk with restart algorithm. Conclusion Based on bioinformatics analysis of a ceRNA network, we identified the lncRNAs H19, GS1-358P8.4, and RP11-96D1.10 as being strongly associated with ovarian endometriosis. These three lncRNAs hold potential as targets for medical therapy and as diagnostic biomarkers. Further studies are needed to elucidate the detailed biological function of these lncRNAs in the pathogenesis of endometriosis.
Acupuncture for Psychological Disorders Caused by Chronic Pain: A Review and Future Directions

Accumulating evidence supports an association between chronic pain and psychological disorders, a connection that seems to be bidirectional. Treating both the pain and psychological conditions together is essential for effective treatment outcomes. Acupuncture is a somatosensory-guided mind–body therapy that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. In this review, we discuss the use of acupuncture in some conditions with a high incidence of psychological disorders caused by chronic pain: headache, musculoskeletal pain, low back pain, and cancer pain, focusing on the effect and potential mechanisms of acupuncture. Overall clinical studies indicated that acupuncture might effectively contribute to management of psychological disorders caused by chronic pain. Mechanistic studies showed that acupuncture significantly alleviated such psychological disorders by regulating the activity of amygdala and insula, and regulating functional connectivity of insular and limbic regions/medial prefrontal cortex in humans and the corresponding animal models. In addition, 5-HT in the dorsal raphe nucleus, opioid receptors in the cingulate cortex, and plasma met-enkephalin are involved in acupuncture relief of pain and psychological symptoms. Substantial evidences from animal and human research support a beneficial effect of acupuncture in psychological disorders caused by chronic pain.
Intravenous and Oral Fluid Therapy in Neonatal Calves With Diarrhea or Sepsis and in Adult Cattle

Optimal fluid therapy protocols in neonatal calves and adult cattle are based on consideration of signalment, history, and physical examination findings, and individually tailored whenever laboratory analysis is available. Measurement of the magnitude of eye recession, duration of skin tenting in the lateral neck region, and urine specific gravity by refractometry provide the best estimates of hydration status in calves and cattle. Intravenous and oral electrolyte solutions (OES) are frequently administered to critically ill calves and adult cattle. Application of physicochemical principles indicates that 0.9% NaCl, Ringer's solution, and 5% dextrose are equally acidifying, lactated Ringer's and acetated Ringer's solution are neutral to mildly acidifying, and 1.3–1.4% sodium bicarbonate solutions are strongly alkalinizing in cattle. Four different crystalloid solutions are recommended for intravenous fluid therapy in dehydrated or septic calves and dehydrated adult cattle: (1) lactated Ringer's solution and acetated Ringer's solution for dehydrated calves, although neither solution is optimized for administration to neonatal calves or adult cattle; (2) isotonic (1.3%) or hypertonic (5.0 or 8.4%) solutions of sodium bicarbonate for the treatment of calves with diarrhea and severe strong ion (metabolic) acidosis and hyponatremia, and adult cattle with acute ruminal acidosis; (3) Ringer's solution for the treatment of metabolic alkalosis in dehydrated adult cattle, particularly lactating dairy cattle; and (4) hypertonic NaCl solutions (7.2%) and an oral electrolyte solution or water load for the rapid resuscitation of dehydrated neonatal calves and adult cattle. Much progress has been made since the 1970's in identifying important attributes of an OES for diarrheic calves. Important components of an OES for neonatal calves are osmolality, sodium concentration, the effective SID that reflects the concentration of alkalinizing agents, and the energy content. The last three factors are intimately tied to the OES osmolality and the abomasal emptying rate, and therefore the rate of sodium delivery to the small intestine and ultimately the rate of resuscitation. An important need in fluid and electrolyte therapy for adult ruminants is formulation of a practical, effective, and inexpensive OES.
Large lakes harbor streamlined free-living nitrifiers

Microbial nitrification is a critical process governing nitrogen availability in aquatic systems and provides energy for aphotic carbon fixation. Nitrifiers are phylogenetically and physiologically diverse, but the factors controlling this diversity, and its biogeochemical implications, are poorly understood, particularly in freshwater systems. Here, we characterized the taxonomic, genomic, and metabolic diversity of free-living nitrifiers across Earth’s largest freshwater system, the Laurentian Great Lakes. Surprisingly, ammonia oxidizing Bacteria (AOB) related to Nitrosospira dominated over ammonia oxidizing Archaea (AOA) at most stations, even in oligotrophic lakes with extremely low substrate concentrations. Nitrite oxidizing Bacteria (NOB) Ca. Nitrotoga and Nitrospira each dominated a subset of stations, even switching within a lake. Among four ecotypes of Nitrosospira we identified, one encodes proteorhodopsin, which could enhance survival of this AOB in transparent, low nutrient lakes. Genome reconstructions for free-living AOA, AOB, and NOB indicate small genomes across all taxa and diverse adaptations to sunlight and oxidative stress. Our findings expand the known functional diversity of nitrifiers and provide the first integrated picture of freshwater nitrifier genomics and ecology. As lakes worldwide undergo rapid environmental change, understanding the relationship between microbial biodiversity and nitrogen cycling is essential for predicting future ecosystem health and services.
KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition

The epithelial-to-mesenchymal transition (EMT) is considered a transcriptional process that induces a switch in cells from a polarized state to a migratory phenotype. Here we show that KSR1 and ERK promote EMT through the preferential translation of Epithelial-Stromal Interaction 1 (EPSTI1), which is required to induce the switch from E-to N-cadherin and coordinate migratory and invasive behavior. EPSTI1 is overexpressed in human colorectal cancer (CRC) cells. Disruption of KSR1 or EPSTI1 significantly impairs cell migration and invasion in vitro, and reverses EMT, in part, by decreasing the expression of N-cadherin and the transcriptional repressors of E-cadherin expression, ZEB1 and Slug. In CRC cells lacking KSR1, ectopic EPSTI1 expression restored the E-to N-cadherin switch, migration, invasion, and anchorage-independent growth. KSR1-dependent induction of EMT via selective translation of mRNAs reveals its underappreciated role in remodeling the translational landscape of CRC cells to promote their migratory and invasive behavior.
Computational and Experimental Approaches to Controlling Bacterial Microcompartment Assembly

Bacterial microcompartments compartmentalize the enzymes that aid chemical and energy production in many bacterial species. These protein organelles are found in various bacterial phyla and are postulated to help many of these organisms survive in hostile environments such as the gut of their hosts. Metabolic engineers are interested in repurposing these organelles for non-native functions. Here, we use computational, theoretical and experimental approaches to determine mechanisms that effectively control microcompartment self-assembly. As a model system, we find via multiscale modeling and mutagenesis studies, the interactions responsible for the binding of hexamer-forming proteins propanediol utilization bacterial microcompartments from Salmonella and establish conditions that form various morphologies. We determine how the changes in the microcompartment hexamer protein preferred angles and interaction strengths can modify the assembled morphologies including the naturally occurring polyhedral microcompartment shape, as well as other extended shapes or quasi-closed shapes. We demonstrate experimentally that such altered strengths and angles are achieved via amino acid mutations. A thermodynamic model that agrees with the coarse-grained simulations provides guidelines to design microcompartments. These findings yield insight in controlled protein assembly and provide principles for assembling microcompartments for biochemical or energy applications as nanoreactors.
T cell self-reactivity during thymic development dictates the timing of positive selection

Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced TCR sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity down-regulate TCR sensitivity more slowly during positive selection, and suggest that modulation of membrane ion channel function may play a role in regulating TCR tuning throughout development. Impact Statement Developing T cells whose TCRs have relatively low reactivity experience very brief TCR signaling events, delayed positive selection, and do not fully down regulate their TCR sensitivity as they mature.
Control over patch encounters changes foraging behaviour

Foraging is a common decision problem in natural environments. When new exploitable sites are always available, a simple optimal strategy is to leave a current site when its return falls below a single average reward rate. Here, we examined foraging in a more structured environment, with a limited number of sites that replenished at different rates and had to be revisited. When participants could choose sites, they visited fast-replenishing sites more often, left sites at higher levels of reward, and achieved a higher net reward rate. Decisions to exploit-or-leave a site were best explained with a computational model that included both the average reward rate for the environment and reward information about the unattended sites. This suggests that unattended sites influence leave decisions, in foraging environments where sites can be revisited. Highlights Being able to select sites during foraging increased visits to high value sites This visitation pattern was efficient, producing higher average reward rates Decisions to leave a site were influenced by information about alternative sites Graphical Abstract
Combined Enhanced Biological Phosphorus Removal (EBPR) and Nitrite Accumulation for Treating High-strength Wastewater

The enhanced biological phosphorus removal (EBPR) has been widely applied in treating domestic wastewater, while the performance on high-strength P wastewater is less investigated and the feasibility of coupling with short-cut nitrogen removal process remains unknown. This study first achieved the simultaneous high-efficient P removal and stable nitrite accumulation in one sequencing batch reactor for treating the synthetic digested manure wastewater. The average effluent P could be down to 0.8 ± 1.0 mg P/L and the P removal efficiency was 99.5 ± 0.8%. Candidatus Accumulibacter was the dominant polyphosphate accumulating organism (PAO) with the relative abundance of 14.2-33.1% in the reactor. Examination of the micro-diversity of Candidatus Accumulibacter using 16s rRNA gene-based oligotyping analysis revealed one unique Accumulibacter oligotype that different from the conventional system, which accounted for 64.2-87.9% of the total Accumulibacter abundance. The presence of high-abundant glycogen accumulating organisms (GAO) (15.6-40.3%, Defluviicoccus and Candidatus Competibacter) did not deteriorate the EBPR performance. Moreover, nitrite accumulation happened in the system with the effluent nitrite up to 20.4 ± 6.4 mg N/L and the nitrite accumulation ratio was nearly 100% maintained for 140 days (420 cycles). Nitrosomonas was the dominant ammonia-oxidizing bacteria with relative abundance of 0.3-2.4% while nitrite-oxidizing bacteria were almost undetected (<0.1%). The introduction of extended anaerobic phase and high volatile fatty acid concentrations were proposed to be the potential selector forces to promote partial nitrification. This is the first study that combined EBPR with nitrite-accumulation for digested manure wastewater treatment, and it provided new sights in strategies to combine the EBPR and short-cut nitrogen removal via nitrite to achieve simultaneous nitrogen and phosphorus removal.