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Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels. Cryoelectron microscopy (cryo-EM) structures of the wild-type and improved GeoCas9 (iGeoCas9) enzymes reveal extended contacts between the WED domain of iGeoCas9 and DNA substrates. Biochemical analysis shows that iGeoCas9 accelerates DNA unwinding to capture substrates under the magnesium-restricted conditions typical of mammalian but not bacterial cells. These findings enabled rational engineering of other Cas9 orthologs to enhance genome-editing levels, pointing to a general strategy for editing enzyme improvement. Together, these results uncover a new role for the Cas9 WED domain in DNA unwinding and demonstrate how accelerated target unwinding dramatically improves Cas9-induced genome-editing activity.

The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 μM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of functional affinity in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.

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Background Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization. Objectives In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified. Methods A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells. Results Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P  = 0.015) and using excessive amounts of alcohol and tobacco (P  = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33–13.86; P  = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05–8.19, P  = 0.031) (n = 160). Conclusions VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted. Systematic Review Registration Open Science Framework (https://doi.org/10.17605/OSF.IO/AJGHX). [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic compelled changes to the structure and organization of many occupational sectors that may impact workers' well-being and work-related symptoms. Objective: To evaluate the effects of workrelated modifications associated with the COVID-19 pandemic on occupational health outcomes and work ability (WA) among a large group of Italian banking employees. Methods: 2,859 employees visited during health surveillance in 2021 were divided into two job groups: front-office (FO) and back-office (BO) workers. Data on conditions associated with office work, psychological distress, WA, and fitness-to-work judgment were analyzed and compared with available pre-COVID (2018-2019) studies. Results: After lockdown, a 28% increase in asthenopia was found in BO, while a 22% and 9% increase in musculoskeletal symptoms was found in BO and FO, respectively. Moreover, a 28% rise in stress-related symptoms and a 17% increase in psychotropic drug consumption were found in both groups. After lockdown, the prevalence of WAI scores moderate/poor decreased by 17% in each group, but no evidence of significantly improved WA emerged for either group. Fitness-to-work judgment without limitations prevalence remained unchanged. Conclusion: The study showed a reduced prevalence of analyzed outcomes compared to that found in the literature at pre-COVID and post-lockdown evaluation. A slight worsening in all outcomes examined post-lockdown was also highlighted in our study. It can be speculated that these results are linked to the measures the Institute took to support employees during the COVID-19 pandemic. Indeed, a comprehensive integration between occupational safety and health promotion practices is recommended to ensure the highest level of safeguarding for workers' well-being. [ABSTRACT FROM AUTHOR]

Madison County of western Tennessee is approximately 100 km southeast of the New Madrid seismic zone and, thus, is subject to potentially dangerous seismic shaking and liquefaction events. Holocene floodplain alluvium and associated Pliocene/Pleistocene terraces of the Forked Deer and Hatchie Rivers cover a large part of Madison County. Underlying these unconsolidated sediments are approximately ~650 m of poorly consolidated Paleogene and Cretaceous terrestrial and marine sediments, which are underlain by Paleozoic limestone bedrock. Uniform regional geology used in the 2014 United States Geological Survey seismic hazard maps assumes a homogenous seismic velocity structure above bedrock. Three-dimensional geologic mapping of the ~700 m of Quaternary, Neogene, Paleogene, and Cretaceous sediments conducted in this study provides a more detailed velocity structure, resulting in a more accurate and detailed map of the expected ground motions in Madison County during future earthquakes. In addition, the surface geologic map reveals regions that are susceptible to liquefaction. This paper discusses the methods used to construct the surface geology map, subsurface structure contour maps, isopach maps, and 3D geologic model used in the seismic hazard and liquefaction hazard analyses of Madison County, Tennessee, and summaries of the results of these analyses are presented. [ABSTRACT FROM AUTHOR]

Small pentamerous floral remains commonly encountered in Middle Miocene lake deposits of the Latah Formation of Washington and Idaho, USA, previously assigned to Diospyros , are here shown to represent an extinct genus. Newly recovered specimens preserve characters of the androecium and pollen that were previously unknown. Remberella microcalyx (Knowlton) gen. et comb. nov. flowers are actinomorphic, with five basally connate petals having an adnate androecium including ten staminodes and ten stamens. The elongate-triangular anthers contain finely rugulate, triaperturate pollen. The combination of pentamerous sympetalous corolla, ten staminodes in two whorls and ten stamens adnate to the corolla indicates affinity with early divergent superasterids, likely the Ericales, with intriguing similarities to Ebenaceae. Although the Miocene flora includes many genera confidently assigned to extant genera, Remberella adds to a growing number of contemporary extinct genera.

Iron delivery to the plasma is closely coupled to erythropoiesis, the production of red blood cells, as this process consumes most of the circulating plasma iron. In response to hemorrhage and other erythropoietic stresses, increased erythropoietin stimulates the production of the hormone erythroferrone (ERFE) by erythrocyte precursors (erythroblasts) developing in erythropoietic tissues. ERFE acts on the liver to inhibit bone morphogenetic protein (BMP) signaling and thereby decrease hepcidin production. Decreased circulating hepcidin concentrations then allow the release of iron from stores and increase iron absorption from the diet. Guided by evolutionary analysis and Alphafold2 protein complex modeling, we used targeted ERFE mutations, deletions, and synthetic ERFE segments together with cell-based bioassays and surface plasmon resonance to probe the structural features required for bioactivity and BMP binding. We define the ERFE active domain and multiple structural features that act together to entrap BMP ligands. In particular, the hydrophobic helical segment 81 to 86 and specifically the highly conserved tryptophan W82 in the N-terminal region are essential for ERFE bioactivity and Alphafold2 modeling places W82 between two tryptophans in its ligands BMP2, BMP6, and the BMP2/6 heterodimer, an interaction similar to those that bind BMPs to their cognate receptors. Finally, we identify the cationic region 96-107 and the globular TNFα-like domain 186-354 as structural determinants of ERFE multimerization that increase the avidity of ERFE for BMP ligands. Collectively, our results provide further insight into the ERFE-mediated inhibition of BMP signaling in response to erythropoietic stress.

p97, also known as valosin-containing protein, is an essential cytosolic AAA+ (ATPases associated with diverse cellular activities) hexamer that unfolds substrate polypeptides to support protein homeostasis and macromolecular disassembly. Distinct sets of p97 adaptors guide cellular functions but their roles in direct control of the hexamer are unclear. The UBXD1 adaptor localizes with p97 in critical mitochondria and lysosome clearance pathways and contains multiple p97-interacting domains. Here we identify UBXD1 as a potent p97 ATPase inhibitor and report structures of intact human p97-UBXD1 complexes that reveal extensive UBXD1 contacts across p97 and an asymmetric remodeling of the hexamer. Conserved VIM, UBX and PUB domains tether adjacent protomers while a connecting strand forms an N-terminal domain lariat with a helix wedged at the interprotomer interface. An additional VIM-connecting helix binds along the second (D2) AAA+ domain. Together, these contacts split the hexamer into a ring-open conformation. Structures, mutagenesis and comparisons to other adaptors further reveal how adaptors containing conserved p97-remodeling motifs regulate p97 ATPase activity and structure.

β-arrestins play a key role in G protein-coupled receptor (GPCR) internalization, trafficking, and signaling. Whether β-arrestins act independently of G protein-mediated signaling has not been fully elucidated. Studies using genome-editing approaches revealed that whereas G proteins are essential for mitogen-activated protein kinase activation by GPCRs., β-arrestins play a more prominent role in signal compartmentalization. However, in the absence of G proteins, GPCRs may not activate β-arrestins, thereby limiting the ability to distinguish G protein from β-arrestin-mediated signaling events. We used β2-adrenergic receptor (β2AR) and its β2AR-C tail mutant expressed in human embryonic kidney 293 cells wildtype or CRISPR-Cas9 gene edited for Gαs, β-arrestin1/2, or GPCR kinases 2/3/5/6 in combination with arrestin conformational sensors to elucidate the interplay between Gαs and β-arrestins in controlling gene expression. We found that Gαs is not required for β2AR and β-arrestin conformational changes, β-arrestin recruitment, and receptor internalization, but that Gαs dictates the GPCR kinase isoforms involved in β-arrestin recruitment. By RNA-Seq analysis, we found that protein kinase A and mitogen-activated protein kinase gene signatures were activated by stimulation of β2AR in wildtype and β-arrestin1/2-KO cells but absent in Gαs-KO cells. These results were validated by re-expressing Gαs in the corresponding KO cells and silencing β-arrestins in wildtype cells. These findings were extended to cellular systems expressing endogenous levels of β2AR. Overall, our results support that Gs is essential for β2AR-promoted protein kinase A and mitogen-activated protein kinase gene expression signatures, whereas β-arrestins initiate signaling events modulating Gαs-driven nuclear transcriptional activity.

In the paper entitled Comparative analysis of employed population and the gross domestic product in Romania and the RomanianWestern Region, by sectors of activity, the dynamics of employed population and gross domestic product before and during the pandemic, respectively the period 2016-2021 has been analysed. Based on the comparative analysis of the employed population in Romania and in the Western Region of the same country, for the period 2016-2018, a dynamic in the primary sector was found, a decrease in the secondary sector and an increase in the tertiary sector. In the period 2019-2021, the employed population,by sector of activity,decreased in the primary sector, was dynamic in the secondary sector and increasedin the tertiary sector. There are significant differences between the average percentages calculated for the WesternRegion compared to Romania, which shows a decrease in the employed population in the primary and tertiary sectors and an increase in the secondary. In terms of gross domestic product in current prices, over the entire period 2016-2021, Romania’s gross domestic product by sectors of activity recorded an increase in the primary and tertiary sectors and a dynamic in the secondary sector. At the level of the Western Region, in the period 2016-2019, in all sectors of activity, the gross domestic product in current prices increased. Due to the emergence of the pandemic in 2020, there are decreases in GDP in current prices in all sectors of activity, but from 2021 onwards the economy recovers, so that its values increased both in Romania and in the Western Region.

In the paper entitled Comparative analysis of employed population and the gross domestic product in Romania and the RomanianWestern Region, by sectors of activity, the dynamics of employed population and gross domestic product before and during the pandemic, respectively the period 2016-2021 has been analysed. Based on the comparative analysis of the employed population in Romania and in the Western Region of the same country, for the period 2016-2018, a dynamic in the primary sector was found, a decrease in the secondary sector and an increase in the tertiary sector. In the period 2019-2021, the employed population, by sector of activity, decreased in the primary sector, was dynamic in the secondary sector and increasedin the tertiary sector. There are significant differences between the average percentages calculated for the WesternRegion compared to Romania, which shows a decrease in the employed population in the primary and tertiary sectors and an increase in the secondary. In terms of gross domestic product in current prices, over the entire period 2016-2021, Romania's gross domestic product by sectors of activity recorded an increase in the primary and tertiary sectors and a dynamic in the secondary sector. At the level of the Western Region, in the period 2016-2019, in all sectors of activity, the gross domestic product in current prices increased. Due to the emergence of the pandemic in 2020, there are decreases in GDP in current prices in all sectors of activity, but from 2021 onwards the economy recovers, so that its values increased both in Romania and in the Western Region. [ABSTRACT FROM AUTHOR]

The Rose Canyon fault is the southern extension of the larger Newport-Inglewood-Rose Canyon fault system, which represents a major structural boundary in the Inner Continental Borderland (ICB) offshore of southern California. Ten to fifteen percent of total plate boundary motion in southern California is thought to be accommodated by the faults of the ICB, but the exact distribution of slip is uncertain. With an onshore segment, the Rose Canyon fault offers an opportunity to measure the slip rate using traditional geodetic methods. In this study, we use Global Positioning System (GPS) surface velocities from a combined campaign and continuous GPS network to constrain elastic models of the Rose Canyon fault. We then compare the observed surface velocities with proposed conceptual models of regional fault connections that facilitate the transfer of slip into the Rose Canyon fault to assess how well the observations are explained by the models. The results of elastic half-space models suggest that the Rose Canyon fault may be slipping toward the higher end of geologic estimates, with the preferred model indicating a slip rate of 2.4 ± 0.5 mm/yr. Although limited in terms of near-fault benchmarks, we find an improved model fit using an asymmetrical elastic half-space model and a higher slip rate, suggesting a potential rheological contrast across the Rose Canyon fault, similar to observations from the northern Newport-Inglewood fault segments. Observed GPS surface velocities, background seismicity, and gravity anomalies south of San Diego Bay point toward a more easterly trace for the Rose Canyon fault, suggesting a possible connection with the San Miguel-Vallecitos fault system. Such a connection could increase the potential rupture lengths of future earthquakes and have important consequences for regional seismic hazards. [ABSTRACT FROM AUTHOR]

Wing venation pattern is particularly important in the taxonomy and classification of insects, especially for fossil material. There are recognized transformation series that apparently often represent a mainstream in the evolutionary trend of the wing venation of Hymenoptera. One notable instance is the gradual reduction of the subcosta veins from multiple branches to their total absence. Herein, we place four new genera and six new species in the family Blasticotomidae (=Xyelotomidae) of Hymenoptera. They are Xyelocerus abruptus sp. nov. Liberitoma tenella gen et sp. nov. Liberitoma compta sp. nov. Liberitoma incompleta sp. nov. Aduantoma insolita gen. et sp. nov. and Apertoma gen. nov. from the Middle Jurassic of China, and Enspeletoma oligocaenica gen. et sp. nov. from the Upper Oligocene of Germany. The newly discovered species of Liberitoma from China possessed a supernumerary hind branch of vein Sc in its forewing, which has apparently never been recorded before in other hymenopterans, and the unique venation pattern of Aduantoma suggests the possibility of two additional steps of vein Sc transformation before its complete loss. Based on the new findings, Blasticotomidae are proposed to be divided into four subfamilies: Blasticotominae Thomson 1871, Dahurotominae subfam. nov. Pseudoxyelocerinae subfam. nov. and Undatominae subfam. nov. [ABSTRACT FROM AUTHOR]

Gosong Beach in Bengkayang, West Kalimantan, is selected as a potential Nuclear Power Plant (NPP) site candidate. Volcanic and intrusive rocks are found in the radius of 150 km from it. Based on IAEA (International Atomic Energy Agency) standard, the main assessment target is volcanic rock that is younger than 10 Ma. However, there are Tertiary volcanic and intrusive rocks next to and cover a wide area around the NPP site that show volcanic activities over the Tertiary period. Therefore, it is necessary to investigate this group of rocks to understand its characteristics. This study aims to characterize the geochemistry and petrology of the Tertiary volcanic and intrusive rocks found in northwestern Kalimantan. The fieldwork was conducted to observe and to take Serantak volcanic rocks, Bawang dacite, Niut volcanics, and Sintang intrusion samples. The XRF and micro-XRF analyses were conducted to characterize the geochemical aspect, while petrography and AMICS analyses were conducted to characterize the mineralogical aspect. The result shows that Serantak volcanic rocks, Bawang dacite, Niut volcanics, and Sintang intrusion are derived from tholeiitic to calc-alkaline as a product of mantel partial melting in the subduction zone which go through fractional crystallization. The volcanic activity was initiated by the rise of primitive parental magma from partial melting in the shallow-depth subducted crust as indicated by the garnet-free HREE pattern, the enrichment of LILE and LREE, and the depleted HREE. The Tertiary magmatism in northwestern Kalimantan was found in a small activity with a small impact on the NPP candidate site at Gosong Beach, Bangkayang. [ABSTRACT FROM AUTHOR]

Statistics anxiety is a significant problem for students' learning experience in the psychological sciences. This article explores a novel teaching methodological approach during the global pandemic to improve students' performance by reducing their statistics anxiety. The subject design and teaching methodological approach were developed based on twenty years of experience taking into consideration the student feedback, while its implementation was aligned with the 5-E's Victorian Teaching and Learning pedagogical Model (VTLM). Moreover, to reduce the statistics anxiety, two sections were embedded in the Learning Management System of the subject: (1) an interactive web-based mindfulness intervention and (2) a head-start 'Ready, Set, Go' information pack. The implementation of these approaches resulted in a better understanding of statistical concepts and utilization of the SPSS software by the majority of the students (80% pass-rate). Consequently, a 6% increase in pass rates and an average of 32% increase in satisfaction scores for each item in the university central survey were observed. While the uniqueness of the first year of COVID-period makes comparisons difficult, it is matched by the urgency of the need for effective interventions to support student success. [ABSTRACT FROM AUTHOR]

FAM86A is a class I lysine methyltransferase (KMT) that generates trimethylation on the eukaryotic translation elongation factor 2 (EEF2) at Lys525. Publicly available data from The Cancer Dependency Map project indicate high dependence of hundreds of human cancer cell lines on FAM86A expression. This classifies FAM86A among numerous other KMTs as potential targets for future anticancer therapies. However, selective inhibition of KMTs by small molecules can be challenging due to high conservation within the S-adenosyl methionine (SAM) cofactor binding domain among KMT subfamilies. Therefore, understanding the unique interactions within each KMT-substrate pair can facilitate developing highly specific inhibitors. The FAM86A gene encodes an N-terminal FAM86 domain of unknown function in addition to its C-terminal methyltransferase domain. Here, we used a combination of X-ray crystallography, the AlphaFold algorithms, and experimental biochemistry to identify an essential role of the FAM86 domain in mediating EEF2 methylation by FAM86A. To facilitate our studies, we also generated a selective EEF2K525 methyl antibody. Overall, this is the first report of a biological function for the FAM86 structural domain in any species and an example of a noncatalytic domain participating in protein lysine methylation. The interaction between the FAM86 domain and EEF2 provides a new strategy for developing a specific FAM86A small molecule inhibitor, and our results provide an example in which modeling a protein-protein interaction with AlphaFold expedites experimental biology.

We have investigated the equilibrium properties and rapid-reaction kinetics of the isolated butyryl-CoA dehydrogenase (bcd) component of the electron-bifurcating crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase (EtfAB-bcd) from Megasphaera elsdenii. We find that a neutral FADH• semiquinone accumulates transiently during both reduction with sodium dithionite and with NADH in the presence of catalytic concentrations of EtfAB. In both cases full reduction of bcd to the hydroquinone is eventually observed, but the accumulation of FADH• indicates that a substantial portion of reduction occurs in sequential one-electron processes rather than a single two-electron event. In rapid-reaction experiments following the reaction of reduced bcd with crotonyl-CoA and oxidized bcd with butyryl-CoA, long-wavelength-absorbing intermediates are observed that are assigned to bcdred:crotonyl-CoA and bcdox:butyryl-CoA charge-transfer complexes, demonstrating their kinetic competence in the course of the reaction. In the presence of crotonyl-CoA there is an accumulation of semiquinone that is unequivocally the anionic FAD•- rather than the neutral FADH• seen in the absence of substrate, indicating that binding of substrate/product results in ionization of the bcd semiquinone. In addition to fully characterizing the rapid-reaction kinetics of both the oxidative and reductive half-reactions, our results demonstrate that one-electron processes play an important role in the reduction of bcd in EtfAB-bcd.

Sprouty-related EVH-1 domain-containing (SPRED) proteins are a family of proteins that negatively regulate the RAS-Mitogen-Activated Protein Kinase (MAPK) pathway, which is involved in the regulation of the mitogenic response and cell proliferation. However, the mechanism by which these proteins affect RAS-MAPK signaling has not been elucidated. Patients with mutations in SPRED give rise to unique disease phenotypes; thus, we hypothesized that distinct interactions across SPRED proteins may account for alternative nodes of regulation. To characterize the SPRED interactome and evaluate how members of the SPRED family function through unique binding partners, we performed affinity purification mass spectrometry. We identified 90-kDa ribosomal S6 kinase 2 (RSK2) as a specific interactor of SPRED2 but not SPRED1 or SPRED3. We identified that the N-terminal kinase domain of RSK2 mediates the interaction between amino acids 123 to 201 of SPRED2. Using X-ray crystallography, we determined the structure of the SPRED2-RSK2 complex and identified the SPRED2 motif, F145A, as critical for interaction. We found that the formation of this interaction is regulated by MAPK signaling events. We also find that this interaction between SPRED2 and RSK2 has functional consequences, whereby the knockdown of SPRED2 resulted in increased phosphorylation of RSK substrates, YB1 and CREB. Furthermore, SPRED2 knockdown hindered phospho-RSK membrane and nuclear subcellular localization. We report that disruption of the SPRED2-RSK complex has effects on RAS-MAPK signaling dynamics. Our analysis reveals that members of the SPRED family have unique protein binding partners and describes the molecular and functional determinants of SPRED2-RSK2 complex dynamics.

Distinctive, reticulately sculptured ellipsoidal endocarp impressions have been discovered in Middle Miocene lake deposits of Idaho and eastern Oregon in the northwestern USA. We describe a new species based on these endocarp impressions and compare them morphologically with previously described extinct and extant species of Sabia (Sabiaceae) using light microscopy and micro-CT scanning. Sabia megacarpa sp. nov. endocarps are distinguished by their large size but resemble other species of Sabia in their asymmetric elliptical shape, reticulate surface ribs, unilocular morphology and gland-dotted endocarp surface. Although Sabia is now native to Southeast Asia and Malesia, the fossil record indicates this genus was formerly present in Europe and North America. The new species indicates that Sabia survived until at least 16 million years ago in western North America.

Many EFL learners believe writing is a hard skill to master. Project-based learning is argued to be an effective solution to the problem. This study is aimed to look at the effect of Project-based learning (PJBL) on English writing skill for Indonesian EFL learners and their perceptions of PJBL. A mixed-method approach was implemented in this study. A pair sample t-test was used in analyzing the quantitative data of the written test while the descriptive-qualitative technique was applied in analyzing the data of the interview. Participants are thirty-nine tertiary students from Universitas Tidar. From the study, Indonesian EFL learners believe project-based learning influenced their writing skill in many ways. The result of this study is that there was a significant difference in project-based learning on English writing skill in pre and post-test for EFL learners which favor the improvement in grammar, vocabulary, organization, and content writing of the text. Project-based learning enhances the learners in linguistics aspects such as vocabulary knowledge, grammatical conventions, and punctuation. Besides, it also enhanced the learners' critical and creative thinking in the process of writing. In addition, project-based learning also motivated the learners to write as they were habituated to the independent learning situations that demand them to follow through all the processes accordingly: not to be left behind. Further studies are suggested to gain a deeper and broader comprehension of project-based learning's effect on student's writing skill.

Many EFL learners believe writing is a hard skill to master. Project-based learning is argued to be an effective solution to the problem. This study is aimed to look at the effect of Project-based learning (PJBL) on English writing skill for Indonesian EFL learners and their perceptions of PJBL. A mixed-method approach was implemented in this study. A pair sample T-test was used in analyzing the quantitative data of the written test while the descriptive-qualitative technique was applied in analyzing the data of the interview. Participants are thirty-nine tertiary students from Universitas Tidar. From the study, Indonesian EFL learners believe project-based learning influenced their writing skill in many ways. The result of this study is that there was a significant difference in project-based learning on English writing skill in pre and post-test for EFL learners which favor the improvement in grammar, vocabulary, organization, and content writing of the text. Project-based learning enhances the learners in linguistics aspects such as vocabulary knowledge, grammatical conventions, and punctuation. Besides, it also enhanced the learners' critical and creative thinking in the process of writing. In addition, project-based learning also motivated the learners to write as they were habituated to the independent learning situations that demand them to follow through all the processes accordingly: not to be left behind. Further studies are suggested to gain a deeper and broader comprehension of project-based learning's effect on student's writing skill. [ABSTRACT FROM AUTHOR]

AbstractInstruction in the theory and performance of music has been part of Australian higher education since the nineteenth century. Using the online content analysis approach, this article analyses current units of study and curricula in each Australian public university that continues to teach music. This study provides a detailed analysis of what is taught and how universities providing music education conceptualize the merit and usefulness of this field of study. Our analysis reveals that music education in Australian public universities remains relatively common, but also identifies the trajectories that music education has followed, including departures from traditional classical performance and music theory to coursework offerings that have been enabled by methodologies prevalent in social and cultural history. Universities offering music education have also tried to position such education as fundamental to securing a career, but offer very little in the way of units aiming to develop a broader understanding of the industry or inculcating career-relevant skills beyond those that are strictly relevant to music making. [ABSTRACT FROM AUTHOR]

With the ongoing amendment of the EU legislation on the treatment of urban wastewater, stricter requirements for the removal of pollutants are expected, which calls for the need for innovative wastewater treatment technologies. Biological systems are still the first choice. A survey of typical bioreactors applied in wastewater treatment is presented. The wastewater treatment objective, biochemical environment, and microbial growth are selected as the main criteria for the classification of these bioreactors. Hydraulic and kinetic aspects are considered, along with the advantages and drawbacks of these bioreactors regarding the selection of the appropriate type of reactor; as well, details regarding the operation of reactors are mentioned. The aim of this paper is to provide operators and designers with a brief overview of the selected traditional and advanced processes, reactors, and technologies for nutrient removal from municipal wastewater. The possibilities and limitations in complying with more strict effluent standards are also discussed. Methods of nutrient recovery are added value. From the evaluation of the published papers, we determine that the currently applied traditional methods for nutrient removal have the potential to also convey the expected stricter limits. [ABSTRACT FROM AUTHOR]

Scottish policy, funding, and quality systems have been tasked to provide "a more coherent and streamlined tertiary education system from the student perspective that delivers the best learning experience for students" (Scottish Funding Council, n.d.). This paper helps to inform this process, by presenting the findings from the second stage of Quality Assurance Agency Enhancement Theme project: Mind the Gap? College Students' Experience of University. This stage investigated the perspectives of staff who support students making the transition from college to university. While there is a relatively broad literature covering the student perspective of this transition, the staff perspective is less well understood. This paper uses the themes developed from the first stage of the project - a qualitative research synthesis on the lived experiences of students (Robertson & Cunningham, 2023) - to investigate staff perceptions of this transition. These themes considered are: (1) the responsibility for enabling effective transition; (2) the extent to which alignment between colleges and universities is achievable or, indeed, desirable; and (3) the extent to which college to university transitions genuinely widen participation. This paper reports the findings from a series of focus groups with university academic staff, university student support staff, and college academic staff from three institutions (two universities and one college). Using theoretical thematic analysis, the paper considers how sectoral, academic, identity and social, and logistical factors affect, or are identified in, the practice of the participants and what this means for the development of policy and practice around a 'coherent tertiary model'. [ABSTRACT FROM AUTHOR]

Articulation plays a key role in widening access to HE, but tailored support is necessary for a smooth transition. Articulating students often see themselves as lacking key skills and express concern at the significant differences between college and university. This case study explores how the academic skills team at the University of Dundee supports articulation through STEP UP: a credit-bearing module designed for students enrolled on a Social Sciences Higher National Certificate (HNC) course at Dundee and Angus College who hold a direct entry place for second year Humanities at the university. A key strength of the STEP UP approach is its emphasis on continuity between college and university, welcoming students to the University during their college year. Students implement feedback on their college writing to complete their first university essay, providing them with a clear link between their college and university assignments. They also reflect on their transition by creating a reflective output and presenting a group project on 'Becoming, Being, and Belonging' as a university student. Rather than adopting a deficit approach, emphasising the 'gap' between college and university, STEP UP empowers students to recognise the skills they have developed during their HNC and identify how to employ these skills at university. As Scottish institutions adjust to the new tertiary landscape, STEP UP demonstrates how emphasising continuity rather than difference can help articulation students develop their sense of belonging at university. [ABSTRACT FROM AUTHOR]

Since 2021, the Quality Assurance Agency (QAA) has been working collaboratively with colleges, universities, sector agencies and the Scottish Funding Council (SFC) to support the development of Scotland's new Tertiary Quality Enhancement Framework (TQEF). In 2023, QAA Scotland was asked by the SFC to oversee design of two key components of the TQEF - an approach to external peer review and follow-up activity, and national thematic enhancement activity. This paper outlines progress so far working with staff and students from across Scotland's colleges and universities, our partner quality and sector agencies, and the SFC. [ABSTRACT FROM AUTHOR]

This study aims to use Bouguer gravity anomalies to create a simple subsurface model of the southeastern Thrace Basin, a Tertiary depositional area located in the Northwest Turkey. Relative gravity data have been collected at over 500 points in the study area, converted into Bouguer gravity anomalies and combined with the Bouguer gravity data available in the literature for the area. The study area is subdivided into eight geological units depending on the ages and densities. A total of 12 gravity profiles were deduced from the gravity map and modelled using 2D structure, then combined into a 3D subsurface model. The observed and the calculated gravity data are highly synchronous with an RMS of ~ 0.2 mGals. Results indicate that the basin has an approximate depth of 4000 m. These findings do not agree with the other studies in literature, which will be discussed. The produced model is the most detailed shallow subsurface model of the area so far, consisting of multiple geological layers. [ABSTRACT FROM AUTHOR]

Of Cenozoic age, the Fossong-Wentcheng trachytic dome is located on the southwestern slope of Mount Bambouto. It was probably emplaced during the second period of activity (between 18.5 and 15.3 Ma) of the Mount Bambouto, within the Pan-African granitic basement rock. The dome shows aphyric and porphyritic textures with crystals such as sanidine, clinopyroxene, and oxides. These oxides may be magnetite due to the dominant ferromagnetic behavior of the rock. The dominance of planar AMS ellipsoids and low Pj values reflect the high viscosity of the magma that sets up the Fossong-Wentcheng trachytic dome. The magnetic fabric (foliation and lineation) displays roughly sub-circular trends in the central and the northern parts of the dome with the feeder zone located on its southern part where they display fabrics in the NE-SW direction with steep dips and plunges. This implies that the magma rose through a NE-SW–directed fracture in the basement granitic rock before its propagation towards the NNW-SSE direction by developing one lobe flow emplacement. [ABSTRACT FROM AUTHOR]

The EtfAB components of two bifurcating flavoprotein systems, the crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase from the bacterium Megasphaera elsdenii and the menaquinone-dependent NADH:ferredoxin oxidoreductase from the archaeon Pyrobaculum aerophilum, have been investigated. With both proteins, we find that removal of the electron-transferring flavin adenine dinucleotide (FAD) moiety from both proteins results in an uncrossing of the reduction potentials of the remaining bifurcating FAD; this significantly stabilizes the otherwise very unstable semiquinone state, which accumulates over the course of reductive titrations with sodium dithionite. Furthermore, reduction of both EtfABs depleted of their electron-transferring FAD by NADH was monophasic with a hyperbolic dependence of reaction rate on the concentration of NADH. On the other hand, NADH reduction of the replete proteins containing the electron-transferring FAD was multiphasic, consisting of a fast phase comparable to that seen with the depleted proteins followed by an intermediate phase that involves significant accumulation of FAD⋅-, again reflecting uncrossing of the half-potentials of the bifurcating FAD. This is then followed by a slow phase that represents the slow reduction of the electron-transferring FAD to FADH-, with reduction of the now fully reoxidized bifurcating FAD by a second equivalent of NADH. We suggest that the crossing and uncrossing of the reduction half-potentials of the bifurcating FAD is due to specific conformational changes that have been structurally characterized.

Background: Poisoning is a major public health problem and due to industrialization and urbanization, its incidence is on a major rise and it may be poisoning, suicidal, accidental, or homicidal. It is extremely important for physicians to have the knowledge of common suicidal poisons in a particular locality as it may help in the early diagnosis and management of acute poisoning cases. Therefore, this study was conducted to know the clinical spectrum of acute poisoning cases in and around Mangaluru and the effectiveness of decontamination procedures. Methods: 100 patients admitted in the intensive care units and wards of the General Medicine department were observed in this study. Details of each of these patients like presenting complaints, time of onset of the symptoms, addictive habits, and the nature of poisons consumed were noted. Clinical parameters such as whether stomach wash was given or not, the time lapse between the consumption of poison and stomach wash, the time lapse between the consumption of poison and stomach wash and death of the patients, duration of hospital stay, psychiatric condition of the patient and overall mortality rate of poisoning cases, were observed in this study. Results and Conclusion: The present study shows that organophosphate poisoning is the commonest type of poisoning. Nausea or vomiting is the most common symptom. There is a significant correlation between the time elapsed between the consumption of poison and stomach wash and mortality. Mortality was highest in patients with paraquat poisoning followed by rat poisoning.

An increasingly complex and demanding research landscape has seen university libraries rapidly evolve their services. While research data management, bibliometrics, and research impact services have predominantly featured in the literature to date, the full scope of support libraries are currently providing to their institutions is unknown. This paper aims to present an up-to-date view of the scope and extent of research support services by university libraries across Australia and Aotearoa New Zealand. A coding process analyzed content data from university library websites. Eleven research support areas were identified. Service delivery is split between synchronous and asynchronous modes. This paper describes a lived experience of an evidence-based library and information practice approach to improving research support services at two Australian university libraries, and while it highlights continued maturation of research support services, more research is needed to better understand influences on service development. [ABSTRACT FROM AUTHOR]

Background: Most maternal deaths are preventable, as the healthcare solutions to prevent or manage complications are well known, yet the global burden is still high in many developing countries, including Nigeria. Although access to healthcare services is the right of every woman around the globe, irrespective of economic position and social group but there is still a low level of maternal health care seeking behavior that is compounded by the extremely low skilled attendants especially in low and middle-income countries. Objective: To assess the maternal healthcare utilization among women of child-bearing ages attending out-patient clinics in all Nnamdi Azikiwe University Teaching Hospital Outstations in Anambra State, South-East, Nigeria. Methodology: After obtaining approval from the ethics and research committees in Nnamdi Azikiwe University Teaching Hospital, a cross-sectional survey of 300 consenting women who met the eligibility criteria was conducted. They were selected by systematic random sampling from 15th February to 15th March, 2021. Data collection was by the use of a self-administered structured questionnaire and analyzed using the statistical package for Social Sciences (SPSS) version 20.0. The level of significance for this study was set at P < 0.05 for all analyses. Results: A total of 300 women with a mean age and standard deviation of 29.4±0.7 years participated in the study. The proportion of respondents who utilized the health care facilities was 252 (84.67%), while 12.67% attended maternity homes and 2.66% preferred to stay at home. Conclusion: Many women did utilize the health care facilities and utilization was influenced by their level of education. Health awareness campaigns should be conducted at the community level to raise the women's level of understanding about the importance of utilization of maternal health services. [ABSTRACT FROM AUTHOR]

Distinctive, reticulately sculptured ellipsoidal endocarp impressions have been discovered in Middle Miocene lake deposits of Idaho and eastern Oregon in the northwestern USA. We describe a new species based on these endocarp impressions and compare them morphologically with previously described extinct and extant species of Sabia (Sabiaceae) using light microscopy and micro-CT scanning. Sabia megacarpa sp. nov. endocarps are distinguished by their large size but resemble other species of Sabia in their asymmetric elliptical shape, reticulate surface ribs, unilocular morphology and gland-dotted endocarp surface. Although Sabia is now native to Southeast Asia and Malesia, the fossil record indicates this genus was formerly present in Europe and North America. The new species indicates that Sabia survived until at least 16 million years ago in western North America. [ABSTRACT FROM AUTHOR]

Tertiary institutions play a critical role in the economic and social development of a country, as they produce a skilled workforce that can contribute to the growth and development of various sectors of the economy for human capacity building. Tertiary institutions in Cross River State, Nigeria are faced with various challenges, including inadequate funding and insufficient resources to support their academic activities. This study explored revenue generation models of financing in the administration of tertiary institutions in Cross River State, Nigeria. Descriptive survey research design was adopted in the study. A sample of 720 respondents made up of all the account and financial officers in tertiary institutions in the study area, was drawn through census approach to participate in the study. A 20-item instrument titled: Revenue Generation Models of Financing Tertiary Institutions Questionnaire (RGMFTIQ) with a reliability index of 0.88 on Cronbach's alpha was used for data collection. This instrument was effectively validated by three (3) experts in the Department of Educational Management University of Calabar. Mean and Standard deviation was used to answer the two (2) research questions, while Multivariate Analysis of Variance (MANOVA) was used to test the hypothesis at .05 alpha level. Findings revealed that those models occur at a low level and could not be accepted as sources of revenue generation in tertiary institutions in the study area. The result of the hypothesis revealed that there were no statistically significant differences in financial and account officers' perception on the revenue generation model as well as in their educational impact domain in tertiary institutions in Cross River State. It was recommended hat tertiary institutions in Cross River State should consider diversifying their revenue sources beyond government funding to enhance their financial sustainability. [ABSTRACT FROM AUTHOR]

This article examines the impact of True Justice, a unique continuing legal education programme introduced in 2022 to increase cultural competency in legal practitioners. The programme achieves its purpose via the incorporation of First Nations principles and pedagogies, taking participants beyond the university classroom to learn deep listening on Country. The feedback from participants in the programme in April and May 2022 reveals the powerful experiences that are possible when the university classroom is abandoned in favour of place-based, trauma-informed learning. Incorporating not only First Nations perspectives but also pedagogies is particularly important in the legal profession, where, if these are ignored, practitioners and educators risk reproducing colonial models. [ABSTRACT FROM AUTHOR]

This study explores how university students in Bangladesh utilize ChatGPT, an AI-powered educational tool. Through a survey of 62 students of an engineering institution, the research uncovers that ChatGPT predominantly aids them in educational tasks, such as homework assistance and test preparation. While appreciated for its convenience, concerns exist among the students about accuracy, reliability, and potential overreliance. This study underscores the potential value of ChatGPT in education if used judiciously, highlighting the importance of striking a balance with conventional learning methods. It also advocates for the formulation of clear usage guidelines in educational institutions and recommends further research to understand the long-term effects on students' learning and academic performance. [ABSTRACT FROM AUTHOR]

TRAAK is a mechanosensitive two-pore domain K+ (K2P) channel localized to nodes of Ranvier in myelinated neurons. TRAAK deletion in mice results in mechanical and thermal allodynia, and gain-of-function mutations cause the human neurodevelopmental disorder FHEIG. TRAAK displays basal and stimulus-gated activities typical of K2Ps, but the mechanistic and structural differences between these modes are unknown. Here, we demonstrate that basal and mechanically gated openings are distinguished by their conductance, kinetics, and structure. Basal openings are low conductance, short duration, and due to a conductive channel conformation with the interior cavity exposed to the surrounding membrane. Mechanically gated openings are high conductance, long duration, and due to a channel conformation in which the interior cavity is sealed to the surrounding membrane. Our results explain how dual modes of activity are produced by a single ion channel and provide a basis for the development of state-selective pharmacology with the potential to treat disease.

Mutation of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal degeneration (FTD), which is attributed to both a gain and loss of function. C9orf72 forms a complex with SMCR8 and WDR41, which was reported to have GTPase activating protein activity toward ARF proteins, RAB8A, and RAB11A. We determined the cryo-EM structure of ARF1-GDP-BeF3- bound to C9orf72:SMCR8:WDR41. The SMCR8longin and C9orf72longin domains form the binding pocket for ARF1. One face of the C9orf72longin domain holds ARF1 in place, while the SMCR8longin positions the catalytic finger Arg147 in the ARF1 active site. Mutations in interfacial residues of ARF1 and C9orf72 reduced or eliminated GAP activity. RAB8A GAP required ~10-fold higher concentrations of the C9orf72 complex than for ARF1. These data support a specific function for the C9orf72 complex as an ARF GAP. The structure also provides a model for the active forms of the longin domain GAPs of FLCN and NPRL2 that regulate the Rag GTPases of the mTORC1 pathway.

The structures of Aspergillus oryzae α-amylase were determined in a tetragonal crystal, having one molecule as asymmetric unit, and a monoclinic crystal with two molecules as asymmetric unit. Both crystal forms were obtained from trace contaminants of an old commercial lipase preparation. Structures were determined and refined to 1.65 Å and 1.43 Å resolution respectively. The latter crystal has a non-crystallographic (NCS) twofold axis within the asymmetric unit. Glycosylation at Asn197 is evident, and in the tetragonal crystal can be seen to include three, partially disordered sugar residues following the initial N-acetyl glucosamine (NAG). Superposition of the tetragonal crystal model on the α-amylases from Bacillus subtilis (PDB:1BAG), pig pancreas (PDB:3L2L), and barley (PDB:1AMY), show a high degree of coincidence, particularly for the (β/α)8-barrel domains, and especially within the active site. Using this structural agreement between amylases, we extrapolated the binding model of a six residue, limit dextrin found in pig pancreas α-amylase to the A. oryzae enzyme model, which predicts substrate interacting amino acid residues.

The rapid increase in the number of proteins in sequence databases and the diversity of their functions challenge computational approaches for automated function prediction. Here, we introduce DeepFRI, a Graph Convolutional Network for predicting protein functions by leveraging sequence features extracted from a protein language model and protein structures. It outperforms current leading methods and sequence-based Convolutional Neural Networks and scales to the size of current sequence repositories. Augmenting the training set of experimental structures with homology models allows us to significantly expand the number of predictable functions. DeepFRI has significant de-noising capability, with only a minor drop in performance when experimental structures are replaced by protein models. Class activation mapping allows function predictions at an unprecedented resolution, allowing site-specific annotations at the residue-level in an automated manner. We show the utility and high performance of our method by annotating structures from the PDB and SWISS-MODEL, making several new confident function predictions. DeepFRI is available as a webserver at https://beta.deepfri.flatironinstitute.org/ .

Abstract Background The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. Methods/Design This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. Discussion This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. Trial Registration NCT05691530 registered on January 20, 2023.

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl- into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation-diffusion process upon light-triggered retinal isomerization.