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The endoplasmic reticulum (ER)-Golgi system has been studied using biochemical, genetic, electron and light microscopic techniques. We now understand many aspects of trafficking from the ER to the Golgi apparatus, including some of the signals and mechanisms for selective retention and retrieval of ER resident proteins and export of cargo proteins. Proteins that leave the ER emerge in ‘export complexes’ or ER ‘exit sites’ and accumulate in pleiomorphic transport carriers referred to sometimes as VTCs or intermediate compartments. These structures then transit from the ER to the Golgi apparatus along microtubules using the dynein/dynactin motor and fuse with the cis cisterna of the Golgi apparatus. Many proteins (including vSNAREs, ERGIC53/p58 and the KDEL receptor) must cycle back to the ER from pre-Golgi intermediates or the Golgi. We will discuss both the currently favored model that this cycling occurs via 50-nm COPI-coated vesicles and in vivo evidence that suggests retrograde trafficking may occur via tubular structures. [ABSTRACT FROM AUTHOR]

Deep biospheric anaerobic microbial sulfate reduction and oxidative sulfur cycling have been studied in long sediment cores mainly acquired as part of IODP explorations. The most remarkable observation in many of these studies is the existence of an active sulfur cycle in the deep subsurface sediments that have very low organic carbon content and are presumably refractory. Here, we investigate the interstitial sulfate concentrations and sulfur isotope ratios in a 290 m-long sediment core collected from the eastern Arabian Sea at a water depth of 2663 m. Continuous decrease in porewater-sulfate concentrations with depth (up to 75 mbsf) coupled with enrichment in δ34SSO4 values suggests organoclastic sulfate reduction (OSR) processes attributed to the activity of sulfate-reducing bacteria (SRB) and retention of labile organic substrates amenable to the SRBs. Below a depth of 75 mbsf, the absence of further reduction in sulfate concentration indicates insufficient labile substrate to drive sulfate-reduction activity. An increase in sulfate concentrations at the deeper subsurface (below 128.5 mbsf) coupled with decreasing δ34SSO4 values may be attributed to the oxidation of Fe-sulfide to sulfate. The increase in porewater alkalinity in the lower part of the core has been linked to the silicate degradation process by CO2 produced via the dissolution of CaCO3. Compilation of previous studies from this core, along with our investigation, intrigues future research on organic matter reactivity and microbiological activity in deeper subsurface under oligotrophic depositional regimes. [ABSTRACT FROM AUTHOR]

This paper employs insights from earth science on the financial risk of project developments to present an economic theory of critical minerals. Our theory posits that back-ended critical mineral projects that have unaddressed technical and non-technical barriers, such as those involving lithium and cobalt, exhibit an additional risk for investors which we term the "back-ended risk premium". We show that the back-ended risk premium increases the cost of capital and, therefore, has the potential to reduce investment in the sector. We posit that the back-ended risk premium may also reduce the gains in productivity expected from artificial intelligence (AI) technologies in the mining sector. Progress in AI may, however, lessen the back-ended risk premium itself by shortening the duration of mining projects and the required rate of investment by reducing the associated risk. We conclude that the best way to reduce the costs associated with energy transition is for governments to invest heavily in AI mining technologies and research. Vespignani and Smyth present an economic theory of risk in critical minerals they term the "back-ended risk premium." They apply AI approaches to reduce this risk premium and lower costs in energy transition. [ABSTRACT FROM AUTHOR]

Background: Psychological readiness is an important consideration for athletes and clinicians when making return to sport decisions following anterior cruciate ligament reconstruction (ACLR). To improve our understanding of the extent of deficits in psychological readiness, a systematic review is necessary. Objective: To investigate psychological readiness (measured via the Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI)) over time after ACL tear and understand if time between injury and surgery, age, and sex are associated with ACL-RSI scores. Methods: Seven databases were searched from the earliest date available to March 22, 2022. Articles reporting ACL-RSI scores after ACL tear were included. Risk of bias was assessed using the ROBINS-I, RoB-2, and RoBANS tools based on the study design. Evidence certainty was assessed for each analysis. Random-effects meta-analyses pooled ACL-RSI scores, stratified by time post-injury and based on treatment approach (i.e., early ACLR, delayed ACLR, and unclear approach). Results: A total of 83 studies were included in this review (78% high risk of bias). Evidence certainty was 'weak' or 'limited' for all analyses. Overall, ACL-RSI scores were higher at 3 to 6 months post-ACLR (mean = 61.5 [95% confidence interval (CI) 58.6, 64.4], I2 = 94%) compared to pre-ACLR (mean = 44.4 [95% CI 38.2, 50.7], I2 = 98%), remained relatively stable, until they reached the highest point 2 to 5 years after ACLR (mean = 70.7 [95% CI 63.0, 78.5], I2 = 98%). Meta-regression suggests shorter time from injury to surgery, male sex, and older age were associated with higher ACL-RSI scores only 3 to 6 months post-ACLR (heterogeneity explained R2 = 47.6%), and this reduced 1–2 years after ACLR (heterogeneity explained R2 = 27.0%). Conclusion: Psychological readiness to return to sport appears to improve early after ACL injury, with little subsequent improvement until ≥ 2-years after ACLR. Longer time from injury to surgery, female sex and older age might be negatively related to ACL-RSI scores 12–24 months after ACLR. Due to the weak evidence quality rating and the considerable importance of psychological readiness for long-term outcomes after ACL injury, there is an urgent need for well-designed studies that maximize internal validity and identify additional prognostic factors for psychological readiness at times critical for return to sport decisions. Registration: Open Science Framework (OSF), https://osf.io/2tezs/. Key Points: Over 70% of studies measuring ACL-RSI scores were judged to have high risk of bias (i.e., low internal validity), leading to a certainty of evidence rating of weak for all analyses. ACL-RSI scores do not appear to increase during typical rehabilitation periods after anterior cruciate ligament reconstruction. Age, sex, and time from injury to surgery (i.e., treatment approach) appear prognostic for early ACL-RSI scores, but their prognostic ability diminishes for later ACL-RSI scores. [ABSTRACT FROM AUTHOR]

This paper examines the impact of gender diversity on financial reporting quality (accrual and real earnings management). We use a sample of 78 Egyptian listed companies over the period 2009–2021. The quality of financial reporting is measured using different models of earnings management (accrual and real earnings management). Accrual earnings management (AEM) is detected through four different models developed by modified Jones model, the Kasznik model, Kothari model, Raman and Shahrur model, while real earnings management (REM) is measured using six different model which are abnormal cash flows from operations (ABCFO), abnormal production costs (ABPROD), abnormal discretionary expenditures (ABDISEXP) and three aggregate proxies (RM1, RM2, RM3). Using the system generalized method of moments, companies with more gender diversity are more effective in reducing accrual earnings manipulation (AEM). The exception is the modified Jones model. Moreover, we find that gender diversity is positively and significantly correlated with financial reporting quality based on proxies of real earnings-based activity, except for RM2. The study found a non-significant and negative relationship between board diversity and RM2 as a proxy for REM. Overall, the empirical results based on accrual and real earnings management models (AEM and REM) support the notion that enterprises with more gender diversity on the board are more effective in controlling earnings manipulation practices. The predictions of corporate governance theories are confirmed. Policy makers should continue to promote and support gender diversity in leadership positions within organizations. This can be achieved through initiatives such as diversity quotas, mentoring programs, and leadership development opportunities for women. [ABSTRACT FROM AUTHOR]

The Golgi Apparatus (GA) is pivotal in vesicle sorting and protein modifications within cells. Traditionally, the GA has been described as a perinuclear organelle consisting of stacked cisternae forming a ribbon-like structure. Changes in the stacked structure or the canonical perinuclear localization of the GA have been referred to as "GA fragmentation", a term widely employed in the literature to describe changes in GA morphology and distribution. However, the precise meaning and function of GA fragmentation remain intricate. This review aims to demystify this enigmatic phenomenon, dissecting the diverse morphological changes observed and their potential contributions to cellular wound repair and regeneration. Through a comprehensive analysis of current research, we hope to pave the way for future advancements in GA research and their important role in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Ferroptosis, a mode of cell death that was recently identified in 2012, is driven by iron-dependent lipid peroxidation and distinct from other mechanisms of cell death such as autophagy and apoptosis. Ferroptosis has the unique features of disruptions in iron equilibrium, iron-induced lipid peroxidation, and the accumulation of glutamate-induced cellular toxicity. The regulation of ferroptosis mainly involves the iron, lipid, and amino acid metabolic pathways, which are controlled by system Xc−, voltage-dependent anion channels, p53 and other pathways. Neurodegenerative diseases involve gradual neuronal loss predominantly within the central nervous system and are categorized into both sporadic and rare hereditary disorders. These diseases result in the progressive decline of specific neuron populations and their interconnections. Recent investigations have revealed a strong correlation between the manifestation and progression of neurodegenerative diseases and ferroptosis. The pharmacological modulation of ferroptosis, whether by induction or inhibition, exhibits promising prospects for therapeutic interventions for these diseases. This review aims to examine the literature on ferroptosis and its implications in various neurodegenerative diseases. We hope to offer novel insights into the potential therapies targeting ferroptosis in central nervous system neurodegenerative diseases. However, there are still limitations of this review. First, despite our efforts to maintain objectivity during our analysis, this review does not cover all the studies on ferroptosis and neurodegenerative diseases. Second, cell death in neurodegenerative diseases is not solely caused by ferroptosis. Future research should focus on the interplay of different cell death mechanisms to better elucidate the specific disease pathogenesis. [ABSTRACT FROM AUTHOR]

Pore pressure (PP) is the most significant and dynamic parameter in reservoir geomechanics, and it optimizes well drilling in the hydrocarbon industry. Improved error accuracy for PP prediction could reduce drilling risk and hazards, and improve wellbore stability and better casing seat selection. Choosing the appropriate mud weight design for an optimized wellbore drilling is another aspect of PP prediction. Initial estimates of the vertical stress (SV) are made in the petrophysical log (especially sonic, density, and resistivity). We attempted to predict PP using four empirical models: the Eaton, Bower, Miller, and Tau models. The magnitudes of SV and PP ranged 25.87–32.72 MPa and 25.31–31.82 MPa, respectively, in the depth interval of 2548.12–2980.02 m, respectively, for linked wells at site National Gas Hydrate Program (NGHP) Expedition-02. In contrast, logging while drilling (LWD) derived actual and predicted pressures were validated with coefficients of determination, R2, varying from 0.995 to 0.998, which were used to evaluate the most precise PP prediction. Further, robust machine learning (ML) techniques, namely artificial neural networks (ANN), decision trees (DT), and support vector regression (SVR), were employed for the prediction of PP using petrophysical log datasets. As a result, numerous datasets were collected from selected wells and applied for model training, testing, and validation. The DT (best-suited) techniques produced the most accurate prediction for PP, with R2 of 0.998. No overpressure generation, whereas normal pressure was monitored in the gas hydrate zone, and slightly higher pressure was experienced in the free gas zone. [ABSTRACT FROM AUTHOR]

The gas hydrate found in the eastern continental margin of India is a boon for this energy-deficient developing country. We used four wells of the National Gas Hydrate Program (NGHP) Expedition 02 from area B of the Krishna–Godavari (KG) basin to estimate gas hydrate saturation. The gas solid hydrate increases the resistivity and sonic velocity of sediment due to its presence. We first used Archie's method to estimate the saturation using deep resistivity log data, assuming that the sedimentary formation is saturated with brine water and gas hydrate only. Then we chose the modified Hashin–Shtrikman upper bound model from the rock physics analysis to estimate saturation from sonic log data using Gassmann's equation. The study of gas hydrate morphology suggests that the gas hydrates are pore-filling and grain-supporting in nature compared with the various rock physics models. Theoretical models were prepared for gas hydrate occurrence in coarser sediments with 25% shale and 75% quartz sediments with the critical porosity being 38%. The porosity above the critical porosity suggests that sediment-saturating fluids control the elastic properties of the formation. We also developed a rock physics template (RPT) for various porosity and gas hydrate saturation scenarios by assuming gas hydrates as a component of the rock matrix and the pore spaces of the sediments saturated by 100% water. The RPT was used to estimate saturations in the four wells. The estimated gas hydrate saturations obtained using the Archie method, rock physics model, and RPT method were compared for all wells, obtaining good agreement with the results. [ABSTRACT FROM AUTHOR]

Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.Protein-protein interactions underlie all aspects of a viral infection. Here the authors employ a pan-viral approach for systematic identification of motif-mediated interactions between viral and human proteins and show that the information can be used to find targets for antiviral drug development. [ABSTRACT FROM AUTHOR]

Research on values has posited that self-transcendence and self-enhancement values are conflicting value types and that an increased focus on one will diminish the emphasis on the other. However, studies in the teaching profession have suggested that these two values may also be compatible, as they can both contribute to better teacher commitment and achievement outcomes. This paradox is a critical knowledge gap that warrants an empirical investigation. Another important gap in value research concerns the role of school values, as past studies have mostly focused on individual values. The current study aimed to resolve the question of whether teachers' self-transcendence and self-enhancement values are conflicting or compatible by examining how these values are associated with each other and how they predict teacher commitment and persistence. The study also took a multilevel perspective by investigating how individual-level and school-level values predict key outcomes. The study involved 1,110 teachers from 40 schools and multilevel structural equation modeling analyses were conducted. The results suggested that teachers' self-enhancement and self-transcendence values can be compatible. These values are positively related to each other and they are also positively associated with higher teacher commitment to school. [ABSTRACT FROM AUTHOR]

Cold seeps are characterized by typical endemic communities with associated microorganisms that depend on sulfide, methane, reduced nitrogenous compounds, and metals as electron donors for their survival through chemosynthesis. The discovery of an active cold seep site in January 2018 in the Krishna-Godavari (K-G) basin of Bay of Bengal was followed by a transit cruise in March 2018 to investigate the distribution and diversity of macrofauna. Further, the ambient sediment and pore water biochemistry were estimated to understand its relationship with macrofauna and the microbial associates of the sediment. Samples were collected at a water depth of around 1750 m at 3 stations: SP1, SP2, and SP3, using the box corer. The benthic fauna at the sites consisted mainly of Bivalvia, shrimps of Caridea family, Gastropoda species, Malacostraca species, Polychaeta, and few species of Echinoidea, Ophiuroidea, and Echiura. A total of 2313 macrofaunal individuals belonging to 8 classes, 18 families, and 20 species were identified from all the three stations. The communities were diverse at these sites with an average Shannon diversity index of 1.64 and are closely related to the lineages previously studied in ecologically similar environments. Most of the macrofauna were found to be filter feeders preferring a low organic carbon environment. Relict vesicomyid clams at the present study site suggest the succession from vesicomyids to the present composition of bivalve mussels and siboglinid worms. The microbial associates in the sediment significantly correlated with methane and hydrogen sulfide concentrations. The study suggests that the K-G basin cold seep serves as a conducive environment for the flourishing of benthic communities and therefore can support a rich biodiversity. [ABSTRACT FROM AUTHOR]

This paper presents an impact evaluation of scholarships, within the Brazilian context, on the scientific performance of Ph.D. holders. The objective is to measure the scholarly production of beneficiaries from FAPESP's (São Paulo Research Foundation) Ph.D. Scholarship Program against unsuccessful applicants. The studied population includes all the individuals who applied for Ph.D. scholarships between 2003 and 2017 and were either granted or rejected by FAPESP. Our evaluation employed a quasi-experimental with ex post facto design. The treatment group comprehends awarded individuals that have completed their Ph.D. degree. The control groups comprehend individuals who: (a) had their application rejected but completed their Ph.D. with scholarships from other funding agencies; and (b) who were rejected but completed their Ph.D. without any scholarship. Additionally, we also conducted an analysis comparing FAPESP awardees with best-rejected individuals. Data collection was carried out for all knowledge fields on large secondary databases (including Scopus and Google Scholar for citations and H-index, Lattes Curriculum Vitae, FAPESP, and CAPES—Coordination of Improvement of Higher Education Personnel). We used exact matching for the analysis. We find that the number of publications, citations, and H-index is higher for FAPESP scholarship holders than for those rejected. The "FAPESP scholarship effect" is much higher when compared to those who did not have support from funding agencies to complete their Ph.D. studies. Therefore, our results vindicate the importance of scholarships for doctoral students to produce qualified scientific knowledge in an emerging economy like Brazil. [ABSTRACT FROM AUTHOR]

In exploration seismology, it is extremely important to enhance the image of the sub-surface in terms of geological features by suppressing the noise. The weighted stacking methods are found to be superior to the conventional stacking and result in good quality seismic images. The weighted stacking process based on principal component analysis (PCA) is employed in the present study to enhance the seismic image from the Krishna-Godavari (KG) basin, India. In present study, the weights are calculated by thresholding the similarities between each data trace and PCA based reference trace. The study demonstrates the efficacy of the method and shows considerable improvement in the resolution of the seismic reflections. The identification of the migration pathways within the gas curtains reported earlier, has become easy and clarity is enhanced for the identification of migration and accumulation of free gas in the downslope region of the seismic image. [ABSTRACT FROM AUTHOR]

The issue of trust in science has come to the fore in recent years. I focus on vaccines, first looking at what is known about trust in vaccines and then concentrating on whether what science education teaches about vaccines can be trusted. I present an argument to connect the phenomenon of vaccine hesitancy to the issue of trust and then argue for what an education about vaccines in school science might look like that takes seriously the notion of respect for students, including students who hold views about vaccination with which science teachers might disagree. Trust in others (people and institutions) varies greatly, both between countries and within countries, and depends on the characteristics of both trustor and trustee, and there are great differences in the extent to which people trust vaccines. However, it is a mistake to think that people who do not trust vaccines are simply ill-informed. There are a range of reasons for rejecting what is often an unexamined narrative about vaccines, namely that vaccines are always desirable. Many people come from communities that have sound reasons for being suspicious of what they are told by governments, business and the medical establishment. COVID-19 and earlier reactions to vaccination health scares show how important high-quality education about vaccines is. Much of that education can take place out of school, but the foundations are laid in school. Vaccine rejection and hesitancy have major global public health implications. Good quality vaccine education should help students understand about relevant biology and the nature of science; it should also be respectful of all students, including those who come from families that reject vaccines or are hesitant about them. [ABSTRACT FROM AUTHOR]

Gas-hydrates, a major unconventional energy resources of the future, are delineated by seismic experiment through the identification of an anomalous reflector, known as the bottom simulating reflector or BSR on seismic data. The amplitude variation with angle (AVA) from the BSR can be used for quantitative assessment of gas-hydrates and free-gas across the BSR. We have performed the AVA analysis of BSR in the Krishna Godavari (KG) basin of India, where gas-hydrates have been recovered in fractured shale by Exp-01 of Indian National Gas Hydrates Program. The study shows negative intercept and positive gradient along two perpendicular seismic lines, one passing through the well at site-10 of Exp-01. The intercept of −0.01 to −0.15 and gradient of 0.01 to 0.4 are interpreted as class-IV anomaly, which is due to anisotropy caused by fractures filled with gas-hydrates. We have modelled the observed AVA pattern using anisotropic equation for horizontally symmetric transversally isotropic (HTI) media in which gas-hydrates occur in the fractures, roughly aligned at angle of 45° above the BSR and patchy gas distribution below the BSR. The results show 0–31% variable gas-hydrates in fractured morphology and 0–11% free gas below the BSR respectively. [ABSTRACT FROM AUTHOR]

We use unsupervised machine learning techniques aided by the Gaussian mixture model (GMM) for clustering downhole data of gas hydrate reservoir in the Andaman Sea, where drilling and coring were done at Site 17 in 2006 under the first expedition of the Indian National Gas Hydrate Programme (NGHP-01). Six different logging data (namely; density, neutron porosity, gamma-ray, resistivity, P- and S-wave velocity) are used in this study. We obtain six clusters using Davies-Bouldin index, Calinski-Harabasz index, Dunn index, dendrogram and self-organizing map, which are verified by high silhouette values. Data are then clustered using k-means, principal component analysis (PCA) and GMM. We notice that the k-means with random initialization gets biased towards the dominant principal component (gamma-ray), whereas, PCA shows each log has optimal weightage. Based on statistical analysis using 100 runs, GMM with the k-means initialization provides better results than GMM with random initialization. However, it provides three possible configurations of six clusters, which become stable when a combination of six logs is used as another input. Six clusters are interpreted in terms of lithology by histogram analysis of the corresponding log values. Lithology is found clay-dominated sediments with little silt and sand, as well as scattered volcanic ash, carbonate ooze, and pyrite, which is consistent with the lithology determined by smear slide and sieve data. Except at a few depths with higher concentrations (20–50%) in volcanic glass and carbonate ooze, gas hydrate occupies about 10% of the pore space in silty-clay sediments with sand and volcanic ash. [ABSTRACT FROM AUTHOR]

Gas hydrate saturation (Sh) is the most challenging key parameter of petrophysical evaluations for reservoir characterization. In total three wells were used (namely, NGHP-01-19, NGHP-01-09, and NGHP-01-08) to compute the petrophysical parameters in the gas hydrate-bearing sediments of the Mahanadi offshore basin. Initially, effective porosity and volume of shale are computed using conventional log data varying from 11–36% and 55–75% respectively. The most prominent technique responding to the physical property has been used to compute the Sh by using Archie's empirical electrical resistivity method. The presence of gas hydrate, free gas, and other lithology affects the sonic velocity which is widely used to quantify the hydrate saturation. Therefore, an attempt is made to quantify the Sh from the wellbore sonic velocity using a rock physics model at higher porosity (∼62%) for unconsolidated marine sediments below the seafloor. The model is best suited for gas hydrate zones where velocity increases with the hydrate saturation but underestimates the saturation for free gas zones below the bottom simulating reflector. In the study area, Sh ranges from 5–13% in the depth interval of 175–200 mbsf for well NGHP-01-19 whereas, small amount of 3–10% and 2–8% for well NGHP-01-09 and NGHP-01-08 respectively. The Sh obtained from the rock physics model is insignificantly mismatched with the saturation obtained from temperature and resistivity data due to the presence of an isotropic layer with fracture filling sediments having anisotropic properties. [ABSTRACT FROM AUTHOR]

Cholesterol is an essential component of plasma membrane and precursor of biological active compounds, including hydroxycholesterols (HCs). HCs regulate cellular homeostasis of cholesterol; they can pass across the membrane and vascular barriers and act distantly as para- and endocrine agents. A small amount of 25-hydroxycholesterol (25-HC) is produced in the endoplasmic reticulum of most cells, where it serves as a potent regulator of the synthesis, intracellular transport, and storage of cholesterol. Production of 25-HC is strongly increased in the macrophages, dendrite cells, and microglia at the inflammatory response. The synthesis of 25-HC can be also upregulated in some neurological disorders, such as Alzheimer's disease, amyotrophic lateral sclerosis, spastic paraplegia type 5, and X-linked adrenoleukodystrophy. However, it is unclear whether 25-HC aggravates these pathologies or has the protective properties. The molecular targets for 25-HC are transcriptional factors (LX receptors, SREBP2, ROR), G protein-coupled receptor (GPR183), ion channels (NMDA receptors, SLO1), adhesive molecules (α5β1 and ανβ3 integrins), and oxysterol-binding proteins. The diversity of 25-HC-binding proteins points to the ability of HC to affect many physiological and pathological processes. In this review, we focused on the regulation of 25-HC production and its universal role in the control of cellular cholesterol homeostasis, as well as the effects of 25-HC as a signaling molecule mediating the influence of inflammation on the processes in the neuromuscular system and brain. Based on the evidence collected, it can be suggested that 25-HC prevents accumulation of cellular cholesterol and serves as a potent modulator of neuroinflammation, synaptic transmission, and myelinization. An increased production of 25-HC in response to a various type of damage can have a protective role and reduce neuronal loss. At the same time, an excess of 25-HC may exert the neurotoxic effects. [ABSTRACT FROM AUTHOR]

Background: Transferrin receptor 1 (TfR1), encoded by TFRC, is a key regulator of iron homeostasis and plays important roles in many diseases, including cancers. Objective: To decipher the underlying molecular functions of TfR1 based on its influence on transcriptome profile in cancer cells. Methods: In this study, we first identified the expression pattern and prognostic influence of TFRC in cervical cancer patients from TCGA database. To explore the regulatory outcomes of TfR1 from the view of whole transcriptome profile, we generated TFRC knockdown (TFRC-KD) HeLa cells and negative control (NC) cells using short hairpin RNA (shRNA) method. Unbiased transcriptome sequencing (RNA-seq) experiment was used to analyze the global expression level and alternative splicing (AS) changes between TFRC-KD and NC cells. Results: We found TFRC was consistently elevated in cervical cancer samples and tightly associated with prognosis of patients. Differential expression analysis revealed that 629 differentially expressed genes (DEGs) were identified between TFRC-KD and NC. Functional enrichment analysis of these DEGs revealed that TFRC-KD extensively disturbed cell physiology related pathways, including immunity, cell metabolism and gene expression. Moreover, dysregulated AS profile also indicated that TfR1 has important roles in the AS regulation. Hundreds of TfR1-regulated AS genes were involved in DNA repair, cell death, transcription and viral reproduction pathways, which were tightly associated with cancer cell progression. Conclusions: In summary, we for the first time explored the molecular functions of TfR1 at transcriptional and post-transcriptional levels. These results demonstrate TfR1 participates in the progression of cervical cancer by affecting the expression and AS levels of genes in cancer associated pathways, which greatly extends our understanding of TfR1 functions besides iron homeostasis and provide novel options in cancer treatment by targeting TfR1. [ABSTRACT FROM AUTHOR]

Analysis of anisotropy from velocity data is essential for improving the hydrocarbon reservoir characterization. The anisotropy of a medium is affected by the mechanical strength, presence of fracture, mineral distribution of the rock, and its degree affects the seismic velocity. We attempted to characterize the anisotropy of the gas hydrate bearing sediments in the offshore Mahanadi basin using three wells. Initially, the presence of anisotropy was investigated by estimating the stiffness coefficients and Thomsen’s parameters (epsilon, gamma and delta) assuming a horizontal transversely medium using dipole S-wave (upper and lower) velocities. The natural fractures were identified from the formation image data. The strong anisotropy is associated with the presence of natural fractures and lower values of the elastic modulus. Most of the strong and weak anisotropy zones are oriented in the NW to W direction of the study area. Our study suggests that the anisotropy in gas hydrate bearing sediment is stress-induced due to the presence of pore filling fractures, and the change of mechanical behavior. The higher positive values of epsilon and delta with gamma represent either dry solid gas hydrate or free gas filled in the fracture of the sediments as observed in the crossplot analysis. Finally, we modeled P-wave and S-wave velocities by incorporating the Thomsen’s parameters. S-wave velocity is less effective than P-wave velocity at 90° angle of fracture relative to the symmetry axis and the modeled P-wave velocity increases upto 2.8% in the gas hydrate bearing sediments. [ABSTRACT FROM AUTHOR]

Medicinal plants are fundamental to health sovereignty, providing vital healthcare and livelihood options for rural mountain communities. We conducted 284 interviews with 416 participants in Badakhshan Province of northeastern Afghanistan focusing on the collection, use, sale, and management of medicinal plants. Participants identified 48 plants within 45 categories of treatment and prevention. The greatest number of plants were used to treat hypertension (14 plants), followed by kidney aids (12), analgesics (11), gastrointestinal aids (11), and dermatological aids (9). Comparisons with hospital records suggest that medicinal plants treat common ailments and preempt the need for some hospital visits. In addition, medicinal plants provide a source of livelihood for approximately 25% of participants. Many gatherers are concerned about the impacts of harvesting on medicinal plant resources. Collaborative research and knowledge exchange are necessary to enhance health sovereignty and community-based stewardship that sustain medicinal plant diversity in the context of increasing commercialization. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (ANP) is a type of peptide hormone secreted by atrial cells, which has many important biological functions and roles. In the current study, we studied the effect of ANP on the activity of epidermal growth factor (EGF). Furthermore, we also explore the cellular properties of EGF in adult retinal pigment epithelial cell line-19 (ARPE-19). For this, we firstly analyzed the cellular properties of EGF on adult retinal pigment epithelial cell line-19 (ARPE-19), the results indicated that EGF/EGFR (epidermal growth factor receptor) internalized into the ARPE-19 cells in a time-dependent manner. In addition, we also found that EGF/EGFR can be transported into the cell nuclei of ARPE-19 in a time-dependent manner in ARPE-19 cells. Furthermore, we analyzed the effect of ANP on EGF's activity, and found that EGFR-mediated signaling was activated with EGF stimulation in a dose-dependent manner, but the intracellular signaling pathways were inhibited by ANP treatment. Additionally, we further analyzed the potential mechanism by which ANP affects the EGF signaling pathway, and the results showed that ANP alone has no effect on total EGFR expression by Western-blot assay. Next, we further evaluated the EGFR stability on the cell membrane, and the results indicated that membrane-localized EGFR expression was significantly down-regulated under ANP treatment, although the total EGFR expression was not changed. In short, the current research lays the foundation for studying the regulatory relationship between ANP and EGF. [ABSTRACT FROM AUTHOR]

Purpose of review: Clinical trials have found that the dapivirine vaginal ring (DVR) is safe to use and effective at reducing women's risk of acquiring HIV infection. As countries prepare for the introduction of this novel long-acting, woman-controlled prevention method, an examination of key learnings from oral pre-exposure prophylaxis (PrEP) delivery will help programs leverage successful innovations and approaches to support DVR scale-up and expand the method mix for HIV prevention. Recent findings: Intensive efforts over the past 5 years have yielded lessons on how to facilitate access to oral PrEP; expand service delivery for PrEP; address the knowledge, attitudes, and skills providers need to support PrEP initiation and effective use; develop messaging that builds community and partner support and combats stigma; and understand the cyclical nature of PrEP use. Summary: Evidence from oral PrEP introduction and scale-up can help inform and expedite DVR introduction. [ABSTRACT FROM AUTHOR]

This conceptual analysis examines the implementation of a state-funded college and career readiness pilot program at a small, rural all-Black school in Illinois. Drawing from ethnographic data that dates from 2010, I offer a retrospective analysis on individual based intervention programming for college and career readiness. Concerned with how young Black high school students are constructed as problems in regards to increasing readiness, I trace policy failure through the theoretical lenses of deficit ideology (Valencia in The evolution of deficit thinking: educational thought and practice, Routledge, New York, 1997) and dysconscious racism (King in J Negro Educ 60(2):133–146, 1991). This analysis illuminates how racism ultimately undermines a-contextual efforts to increase readiness for college and career. [ABSTRACT FROM AUTHOR]

India is not an exception among the countries intensely probing for alternate unconventional hydrocarbon resources in the present day scenario of increasing demand for energy and faster depletion of conventional fossil fuel. It is estimated that in India, the prospects for unconventional hydrocarbons are more than the conventional ones; yet, due to lack of proper studies, non-availability of in-house technologies, and several other socio-economic factors, these deposits were not seriously considered for commercial production. In India's latest energy policy and the 'Atma Nirbhar Bharat Abhiyaan,' various incentives are given to enhance the domestic production of hydrocarbons; thus, many new initiatives are taken to boost the unconventional resources exploration program. CSIR-NGRI initiated its exploration program in 1970 with deep seismic studies. Since then, seismic exploration studies were carried out in various lignite and coal fields, i.e., in Rajasthan, Andhra Pradesh, West Bengal, Madhya Pradesh, Jharkhand, and the Odisha state of India. In the last two decades, CSIR-NGRI made remarkable progress in unconventional resource exploration. Various prospective basins were explored using seismic reflection data to map unconventional resources like Gas hydrates, Coal Bed Methane, and Shale gas. This article presents a brief overview of seismic exploration studies being carried out at CSIR-NGRI to map unconventional hydrocarbons in the sedimentary basins of India. [ABSTRACT FROM AUTHOR]

With the development of the national economy and the advancement of science and technology, wireless sensor networks (WSN), as one of the neural terminals of the Internet of Things, have made great progress and are more widely used in fields such as data collection and industrial control. In daily life, with the development of embedded technology, wireless communication network technology, decentralized information processing, and sensor technology, new technologies have gradually formed, thereby providing new methods for acquiring, processing, and sending information. This paper takes soil composition as the research object and studies the relationship between soil composition and capacitance value according to the difference in dielectric constant of soil, water, and air. The performance and output of the sensor ring detection structure under different soil components (dielectric constants) were measured, which showed that the soil components can be clearly measured by the electrostatic capacity value, and a relatively reliable soil profile component sensor and its System design scheme. Finally, the designed system will be tested on site to prove the feasibility of the scheme. For the growth of crops, the role of water cannot be underestimated, and the importance of water conservancy projects cannot be ignored. Otherwise, it will bring a lagging effect to the increase in agricultural output and income, farmers' income, and agricultural development. On the basis of clarifying the significance of water-saving project construction, analyze the factors that hinder the development of water-saving projects and water-saving technologies, and put forward suggestions to promote the construction of agricultural water conservation projects and the rational use of water resources. [ABSTRACT FROM AUTHOR]

Nanomembrane is an independent structure with a thickness of 1–100 nm and with much large lateral dimensions. Due to the unique properties of nanomembranes, research on the category of structures is valuable. Furthermore, nanomembranes have received a lot of attention from scientists because those types of structures can be used in various bioengineering branches. However, biocompatibility and toxicity of nanomembranes are not fully understood yet. In terms of mechanical engineering, nanomembranes must have mechanical strength, surface treatment to ensure the required structure. Mechanical properties can be affected through the material, fabrication method, porosity. For the application of nanomembranes in bioengineering, it is important to develop research to improve the biocompatibility and mechanical strength of nanomembranes. In this paper, according to the recent achievements, classification of materials, fabrication methods, and porosity are reviewed and summarized. Applications of nanomaterials in tissue engineering (bone and skin) as well as in drug delivery systems are also presented. The aim of the paper is to highlight the role of synthetic nanomembranes in the context of nanotechnologies and provide applications of functionalized nanomembranes in bioengineering. Before continuing noble and costly research, it is necessary to know the key principles and references for understanding progress of nanomembranes over the past decade. [ABSTRACT FROM AUTHOR]

Driven by economic globalization and the development of a low-carbon economy, the Internet of Things has brought new hope to countries around the world. In the context of climate change and rapid urbanization, the health of rivers in coastal areas of China is facing huge risks. The water cycle in coastal areas is complex and highly dependent on human activities. At the same time, the relative lack of long-term measured hydrological data makes it difficult to model the flow of coastal rivers, and also difficult to predict and analyze water quality. Therefore, this paper establishes a method to evaluate the latent heat structure based on the percentage of precipitation or the occurrence frequency of various systems in order to quantify the time, space distribution, and climatic conditions of the latent heat structure of the deep convective system under different regions and weather conditions. In addition, this research first analyzes the rainfall distribution rules and rainfall characteristics in coastal areas, then compares the physical mechanism-based SOBEK hydrological model with the neural network model, and conducts modeling and model characteristics analysis of the coastal areas. In response to these challenges, this article first analyzes and summarizes the temporal and spatial distribution of coastal rainfall and typical rainfall characteristics. This article focuses on the intelligent data mining push service system used by academic libraries at home and abroad. After careful research, academic libraries based on data mining will promote the development of intelligent push services. With the help of SQLServer2019 database management system, Android technology, and PHP component architecture, combined with collaborative filtering algorithms, intelligent book recommendation is realized. The recommendation principle is based on user characteristics and effectively promotes interest classification to create recommendation models and service systems. [ABSTRACT FROM AUTHOR]

Gas hydrates from the continental margin settings are mostly confined to continental slopes. The free gas occurring below the gas hydrate laden sediments play a crucial role in the submarine slope failures and can potentially trigger the submarine landslides. The present study is carried out to investigate such a scenario in the shale dominated Krishna–Godavari (KG) basin having proven gas hydrate deposits. Shale reservoirs are less permeable compared to sandstone reservoirs and as such, the free gas that is locked in the pore spaces of shales would eventually create hydro fractures or faults to escape from the pore spaces. This overpressure from the gas zone will find a pathway to reach the shallower depths. In the present study, two faults are identified of which, one is acting as a potential pathway for overpressures to travel through it, while the other is found to be critically pressurized due to the gas zone below it. The calculated gas column height is ~51 m and any further increase in the gas column height would create a fault slip and cause the mechanical failure of the sediments, creating another potential pathway. We infer that these faults are acting as a migration pathway in our study area and the advection of fluid/gas from the gas zone via the pathway might have played a major role in creating a slope break above the fault. Research highlights: Gas migration and role of free gas on slope stability. Seismic attributes for characterization of free gas zones and migration pathways Gas column height and critical gas pressure necessary to initiate fault activation. Active and passive faults and their role as migration pathways. [ABSTRACT FROM AUTHOR]

Biomaterial based scaffolds for treating large bone defects require excellent biocompatibility and osteoconductivity. Here we report on the fabrication of hydroxyapatite-dendritic mesoporous silica nanoparticles (HA-DMSN) based scaffolds with hierarchical micro-pores (5 µm) and nano-pores (6.4 nm), and their application for bone regeneration. The in vitro studies demonstrated good biocompatibility of dissolution extracts, as well as enhanced osteogenic potential indicated by dose-dependent upregulation of bone marker gene expression (osteocalcin gene (OCN), osteopontin gene (OPN), collagen type I alpha 1 gene (CoL1A1), runt-related transcription factor 2 gene (RUNX2), and integrin-binding sialoprotein gene (IBSP)), alkaline phosphatise (ALP) activity, and alizarin red staining. The in vivo studies showed that HA-DMSN scaffolds significantly increased bone formation in a rat cranial bone defect model after 4 weeks healing. Our study provides a simple method to fabricate promising inorganic scaffolds with hierarchical pores for bone tissue engineering. [ABSTRACT FROM AUTHOR]

We have identified the lithologies from well logs and available core data through the cluster and neural network analysis in the Krishna-Godavari (KG) basin. The unsupervised hierarchical cluster analysis (HCA) has been used to find out the dissimilarity behaviour of pairwise well log data associated with each lithological unit as a measure of proximity. Whereas, supervised neural network analysis has been used for the identification of lithologies of un-cored portion of well using the wireline logs and associated lithologies identified from cores in the same or nearby well. Initially, the persistence behaviour of the wireline logs is confirmed by rescaled range (R/S) analysis. These log data follow a local trend of lithological variation and hence can be used for lithology identification. Subsequently, we have used HCA and multi-layer feed forward (MLF) neural network to envisage the lithological sequence of varying thickness (thick beds of the order of 6 m; thin beds up to 0.3048 m) through the analysis of gamma-ray, bulk density (RHOB), neutron porosity (Φ), sonic transit time (Δt) and photoelectric factor downhole logs. The results using the log data from the Expedition 02 of Indian National Gas Hydrates Program (NGHP-Exp.-02) demonstrate that these non-traditional approaches are suitable for analysing formation lithologies where core data associated with discriminating finer beds are available. The HCA and MLF network-predicted lithologies, made in this study, match realistically with the core derived lithologies, demonstrating their efficacy. Thus, the approach is quite useful for providing quick and accurate information on subsurface lithologies. [ABSTRACT FROM AUTHOR]

Artificial neural network (ANN)–based workflow has been applied to the multi-channel seismic reflection data from the Krishna-Godavari (K-G) basin on the Eastern continental margin of India for delineation of prominent structural features such as chimneys and faults. To eliminate the noise and enhance the data quality, the seismic data is conditioned and filtered by data-conditioning techniques such as dip-steered and structural filters. A single attribute is not sufficient for the delineation of structures such as faults and chimneys; hence, an amalgamation of multiple attributes is necessary for the enhancement of laterally continuous seismic events. Hence, multi-attributes such as dip variance, curvature, coherency, energy, similarity, instantaneous frequency, and frequency washout ratio are extracted from the conditioned data which were combined and fed as inputs for the ANN for the chimney and fault detection. The neural network is trained at the identified chimney/non-chimney and fault/non-fault locations, which generates a final output, namely chimney probability attribute and a fault probability attribute, revealing an improved visibility of faults and chimneys in the seismic data. This multi-attribute approach shows more reliability in comparison with individual attribute responses, which helps in better structural interpretation. The study presents a workflow for better visualization of the subsurface structural features which thereby helps in detailed structural interpretation of the seismic data. [ABSTRACT FROM AUTHOR]

The development of nanoparticle probes has opened up new possibilities for molecular imaging in the era of precision medicine. There are a wide range of nanoprobes that are being used for various modalities that have demonstrated promising potential in early detection, disease monitoring, and theranostics. However, the rate of successful clinical translation of the nanoprobes is very low and is affected by the lack of our understanding about nanoparticle interaction with biological fluids after systemic administration, thus representing an unmet clinical need. One of the poorly understood issues relates to the formation of biomolecular corona, a layer of biomolecules formed on the surface of nanoscale materials during their interactions with biological fluids. The biomolecular corona has several significant effects on the biodistribution of nanoprobes and their imaging ability by (i) reducing their targeting efficacy and (ii) affecting the intrinsic imaging properties (e.g., contrast capacity of magnetic nanoprobes). This review provides insights on the importance of considering biomolecular corona in the development of nanoprobes, which may enable their more efficient utilization for molecular imaging applications. [ABSTRACT FROM AUTHOR]

This paper empirically investigates the financial stability of the countries having both Islamic and conventional banks versus the countries having only conventional banks. It also examines the ability of Islamic banks to provide stability to the overall financial system. The analysis is carried out for a sample of 416 banks drawn from 39 countries over the period 1995–2014. The results provide sound evidence that the dual banking system is more stable than the single banking system. Higher stability is attributed to the presence of Islamic banks in the dual banking system. Furthermore, when only the dual banking system is investigated, the results strongly confirm the greater stability of Islamic banks as compared to their conventional counterparts. Although Islamic banks are mimicking conventional banking practices, their increased interactions with the real economy, investments in real assets, non-aggressive lending profile, and limited exposures to speculative activities make them more resilient and protected. [ABSTRACT FROM AUTHOR]

Epidermal growth factor regulates cell proliferation and migration by binding and activating the extracellular region of its receptor. Many engineered EGFs with enhanced agonist activity are produced, yet the short half-life and poor environmental tolerance of EGF limits its physiological application. By using a more stable porcine EGF as the template in the staggered extension process, two mutants of human and porcine EGF, hL8P and pP8L, were obtained with improved targeting towards normal cells. The comparative studies of hEGF and mutants were conducted to evaluate their activities as agonists. The mutants showed specificity for the proliferation and migration of normal and cancer cells, i.e. both pP8L and hL8P promoted the proliferation and migration of normal cells while delayed that of cancer cells. Both mutants preserved the structure thermostability of hEGF and pP8L showed improved acidic tolerance than hEGF. For the metabolism analysis in HEK293T cells, hL8P and pP8L demonstrated the lower rate of both mutants-EGFR internalization and biodegradation, but higher recycling to the cell surface. This study not only enhanced EGF agonist activity without loss of endurance but also provided a new application foreground for trauma therapy and cancer targeting therapy. [ABSTRACT FROM AUTHOR]

Growth factor receptor-bound 2 (Grb2) is an important link in the receptor tyrosine kinase signaling cascades. It is involved in crucial processes, both physiological (mainly embryogenesis) and pathological (different types of cancer). Several binding partners of all three domains (SH3–SH2–SH3) of this adaptor protein are well described, such as ErbB family members for the SH2 domain and Sos for the SH3 domains. How the different domains interact with each other, both structurally and functionally, is still unclear. These interactions could be essential for regulation processes, and therefore are of great interest. Although a lot of structural data on Grb2 exist, they describe either individual domains, ligand-bound conformations, or frozen pictures of the protein captured by crystallography. Here we report the assignment of backbone and of 13 C β chemical shifts of full-length, apo-Grb2 in solution. In addition to the assigned conformation corresponding to three well-folded domains, a set of peaks compatible with the presence of an unfolded conformation of the N-terminal SH3 domain is observed. This assignment paves the way for future studies of inter-domain interactions and dynamics that have to be taken into account when studying the regulation of Grb2 interactions and signaling pathways. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is an integral surface protein mediating cellular response to a number of growth factors. Its overexpression and increased activation due to mutations is one of the most common traits of many types of cancer. Development and clinical use of the agents, which block EGFR activation, became a prime example of the personalized targeted medicine. However, despite the obvious success in this area, cancer cure remains unattainable in most cases. Because of that, as well as the result of the search for possible ways to overcome the difficulties of treatment, a huge number of new treatment methods relying on the use of EGFR overexpression and its changes to destroy cancer cells. Modern data on the structure, functioning, and intracellular transport of EGFR, its natural ligands, as well as signaling cascades triggered by the EGFR activation, peculiarities of the EGFR expression and activation in oncological disorders, as well as applied therapeutic approaches aimed at blocking EGFR signaling pathway are summarized and analyzed in this review. Approaches to the targeted delivery of various chemotherapeutic agents, radionuclides, immunotoxins, photosensitizers, as well as the prospects for gene therapy aimed at cancer cells with EGFR overexpression are reviewed in detail. It should be noted that increasing attention is being paid nowadays to the development of multifunctional systems, either carrying several different active agents, or possessing several environment-dependent transport functions. Potentials of the systems based on receptor-mediated endocytosis of EGFR and their possible advantages and limitations are discussed. [ABSTRACT FROM AUTHOR]

We conducted a detailed rock magnetic study complemented by sedimentological and mineralogical methods on a 177.2-m-long sediment core of Hole NGHP-01-14A to constrain the influence of high-energy depositional environment on the magnetic mineral diagenesis and formation of gas hydrates in the Krishna-Godavari (K-G) basin, Bay of Bengal. Five sediment magnetic zones were identified based on the downcore variation in rock magnetic parameters. The magnetic mineralogies comprised of detrital titanomagnetite, diagenetically formed magnetic iron sulfides and their mixture. A distinct magnetically enhanced zone (Z-3) close to a bottom simulating reflector (BSR) is dominated by higher magnetite content, sediment bulk density, and grain size and probably represents several sand-rich sediment layers formed as a result of short-duration intense sedimentation events and got rapidly buried and provided conducive environment for the formation of gas hydrate deposits at the studied site. The concurrence of gas hydrates and high gas saturations within the sand-rich layers (Z-3) suggests that the high-energy depositional environment had a larger control over hydrate formation at Hole NGHP-01-14A. Two magnetic iron sulfide bearing sediment intervals in Z-1b and Z-1c below sulfate-methane transition zone (SMTZ) suggest that their formation is controlled by microbially mediated diagenetic reactions fuelled by presence of gas hydrates and probably represents the fossil gas hydrate zones. We propose that the rock magnetic variations in the studied sediment core at Hole NGHP-01-14A is controlled by both differential loading of detrital magnetic minerals as well as hydrate-induced late diagenetic magnetic iron sulfide formation. [ABSTRACT FROM AUTHOR]

Shallow sediments across large parts of Krishna-Godavari (K-G) basin offshore east central Indian contain abundant methane and gas hydrates. In this study, we carried out rock-magnetic and transmission electron microscope (TEM) analyses on the samples from a sediment core (MD161/Stn-8) to constrain the formation and preservation of greigite in shallow sediments and how this might link to reactions involving methane. Here, we report for the first time the occurrence of silicate-hosted iron sulfide (greigite) inclusions which is an important observation for understanding the preservation of magnetic minerals in gas hydrate systems. The magnetization of the greigite zone (17–23 mbsf) is carried by complex magnetic mineral assemblages of detrital iron oxides (titanomagnetite), diagenetic iron sulfide (greigite) occurring as nano-inclusions within larger silicate particles, and biogenic minerals. Elevated concentrations of dissolved pore water silica and alkalinity within the magnetically enhanced greigite zone suggest that silica diagenesis and silicate weathering triggered by paleo-methane seepage played a key role in crystallizing the diagenetically formed iron sulfide (greigite) into silicate matrix. The silicate-hosted magnetic inclusions protected the ferrimagnetic greigite from further diagenetic dissolution and prevented its conversion into stable pyrite. Three scenarios explaining the potential controls on the greigite preservation in gas hydrate marine sedimentary system have been proposed. [ABSTRACT FROM AUTHOR]

This review analyzes and summarizes some actual models of raft organization as dynamic structural units in lipid membranes emphasizing the discrimination between mechanisms influencing raft nanodomain formation and maintenance in biological and model membranes on one hand and the roles of membrane proteins on the other. The contentious issue of specific input of cholesterol recognizing/interacting amino acid consensus (CRAC) motifs in the membrane rafts and protein interaction mechanism at the molecular level is discussed in detail. Especially, lipid membrane raft-like structure of some enveloped viruses is considered as a manifest example demonstrating the basic organization of raft-type membranes. [ABSTRACT FROM AUTHOR]

The production of pore-forming toxins that disrupt the plasma membrane of host cells is a common virulence strategy for bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA)1–3. It is unclear, however, whether host species possess innate immune mechanisms that can neutralize pore-forming toxins during infection. We previously showed that the autophagy protein ATG16L1 is necessary for protection against MRSA strains encoding α-toxin4—a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues2,5,6. Autophagy typically involves the targeting of cytosolic material to the lysosome for degradation. Here we demonstrate that ATG16L1 and other ATG proteins mediate protection against α-toxin through the release of ADAM10 on exosomes—extracellular vesicles of endosomal origin. Bacterial DNA and CpG DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice. Transferred exosomes protect host cells in vitro by serving as scavengers that can bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. These findings indicate that ATG proteins mediate a previously unknown form of defence in response to infection, facilitating the release of exosomes that serve as decoys for bacterially produced toxins. In response to infection with Staphylococcus aureus in vitro and in vivo, host cells increase their secretion of exosomes containing ADAM10—vesicular structures that can provide protection by sequestering bacterial toxins. [ABSTRACT FROM AUTHOR]

Disappearance of many elongated benthic foraminifera across the Mid-Pleistocene Transition (MPT) is popularly known as ‘Stilostomella extinction’. This event is reported from several sites across the world and it is believed that most of the elongated benthic families disappeared within 0.76–0.5 Ma. It is assumed that the presence of cold bottom water triggered their disappearance. The present study is pursued on sediment cores collected from National Gas Hydrate Program Hole 17A, Andaman Sea, Indian Ocean to examine the precise timing and cause of the disappearance of elongated taxa as well as their ecological preference. Our study reveals that elongated species prefer warm and low to intermediate food condition. This study documents the disappearance of 5 major species and 13 minor species from 0.6 to 0.2 Ma which is younger than the earlier estimates. We assume that change in 41–100 kyr climatic cycle along the MPT was responsible for a major decline in their number. However, amplified glacial–interglacial cycles along Mid-Brunhes (0.5–0.2 Ma) finally played a major role in their disappearance. Both of these consecutive events extended intensified cooling and dropped the deep-ocean temperature by which the shallow infaunal elongated species disappeared and deep-infaunal species survived. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin complex 1 (mTORC1) senses and relays environmental signals from growth factors and nutrients to metabolic networks and adaptive cellular systems to control the synthesis and breakdown of macromolecules; however, beyond inducing de novo lipid synthesis, the role of mTORC1 in controlling cellular lipid content remains poorly understood. Here we show that inhibition of mTORC1 via small molecule inhibitors or nutrient deprivation leads to the accumulation of intracellular triglycerides in both cultured cells and a mouse tumor model. The elevated triglyceride pool following mTORC1 inhibition stems from the lysosome-dependent, but autophagy-independent, hydrolysis of phospholipid fatty acids. The liberated fatty acids are available for either triglyceride synthesis or β-oxidation. Distinct from the established role of mTORC1 activation in promoting de novo lipid synthesis, our data indicate that mTORC1 inhibition triggers membrane phospholipid trafficking to the lysosome for catabolism and an adaptive shift in the use of constituent fatty acids for storage or energy production., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The mammalian Golgi apparatus is a highly dynamic organelle, which is normally localized in the juxtanuclear space and plays an essential role in the regulation of cellular homeostasis. While posttranslational modification of cargo is mediated by the resident enzymes (glycosyltransferases, glycosidases, and kinases), the ribbon structure of Golgi and its cisternal stacking mostly rely on the cooperation of coiled-coil matrix golgins. Among them, giantin, GM130, and GRASPs are unique, because they form a tripartite complex and serve as Golgi docking sites for cargo delivered from the endoplasmic reticulum (ER). Golgi undergoes significant disorganization in many pathologies associated with a block of the ER-to-Golgi or intra-Golgi transport, including cancer, different neurological diseases, alcoholic liver damage, ischemic stress, viral infections, etc. In addition, Golgi fragments during apoptosis and mitosis. Here, we summarize and analyze clinically relevant observations indicating that Golgi fragmentation is associated with the selective loss of Golgi residency for some enzymes and, conversely, with the relocation of some cytoplasmic proteins to the Golgi. The central concept is that ER and Golgi stresses impair giantin docking site but have no impact on the GM130-GRASP65 complex, thus inducing mislocalization of giantin-sensitive enzymes only. This cardinally changes the processing of proteins by eliminating the pathways controlled by the missing enzymes and by activating the processes now driven by the GM130-GRASP65-dependent proteins. This type of Golgi disorganization is different from the one induced by the cytoskeleton alteration, which despite Golgi de-centralization, neither impairs function of golgins nor alters trafficking. [ABSTRACT FROM AUTHOR]

Clathrates are inclusion compounds formed by specific host molecules and elements such as water, silica, and silicon in the presence of suitably sized guest molecules at appropriate temperature and pressure conditions. Clathrate compounds are of fundamental importance as they illustrate how simple molecules can combine to form a variety of complex caged structures yielding unique and interesting properties. In this overview, structure, properties, and applications of clathrates formed by silica (called clathrasils) and water (called gas hydrates) are briefly reviewed. Similarities and differences between clathrasils and gas hydrates are discussed with the hope that cross-fertilization between these fields can result in future advancements and new science understanding guest–host crystalline structures. [ABSTRACT FROM AUTHOR]