Early Region Research Articles

Dating the Justinianic Plague in England: integrating historical and archaeological data on the early Cambridgeshire region

ABSTRACT Archaeogenetic analysis has retrieved evidence of the presence of Yersinia pestis, the pathogen of bubonic plague, from graves in the Early Anglo-Saxon cemetery at Edix Hill, Cambridgeshire. Associated grave goods there, and some radiocarbon dates from Germany, suggested that the plague may have been present before the historically recorded outbreak of the 540s known as the Justinianic Plague. Targeted high-precision radiocarbon dating, however, largely confirms the conventional historical chronology. Concurrent re-examination of multiple methodological and empirical issues informatively reveals complex issues within radiocarbon data, and significant disjunctions in the phased sequence of both female and male accoutrements in this part of Anglo-Saxon England across the middle of the sixth century, when the populations were also having to accommodate themselves to the onset of the Late Antique Little Ice Age.

JC virus small tumor antigen promotes S phase entry and cell cycle progression

The early coding region of JC virus (JCV) encodes several regulatory proteins including large T antigen (LT-Ag), small t antigen (Sm t-Ag) and T’ proteins because of the alternative splicing of the pre-mRNA. LT-Ag plays a critical role in cell transformation by targeting the key cell cycle regulatory proteins including p53 and pRb, however, the role of Sm t-Ag in this process remains elusive. Here, we investigated the effect of Sm t-Ag on the cell cycle progression and demonstrated that it facilitates S phase entry and exit when cells are released from G0/G1 growth arrest. Examination of the cell cycle stage specific expression profiles of the selected cyclins and cyclin-dependent kinases, including those active at the G1/S and G2/M transition state, demonstrated a higher level of early expression of these regulators such as cyclin B, cycling E, and Cdk2. In addition, analysis of the effect of Sm t-Ag on the growth promoting pathways including those active in the PI3K/Akt/mTOR axis showed substantially higher levels of the phosphorylated-Akt, -Gsk3-β and -S6K1 in Sm t-Ag-positive cells. Collectively, our results demonstrate that Sm t-Ag promotes cell cycle progression by activating the growth promoting pathways through which it may contribute to LT-Ag-mediated cell transformation.

Development and Characterization of an Oncolytic Human Adenovirus-Based Vector Co-Expressing the Adenovirus Death Protein and p14 Fusion-Associated Small Transmembrane Fusogenic Protein.

Human adenovirus (HAdV)-based oncolytic vectors, which are designed to preferentially replicate in and kill cancer cells, have shown modest efficacy in human clinical trials in part due to poor viral distribution throughout the tumor mass. Previously, we showed that expression of the p14 fusion-associated small transmembrane (FAST) fusogenic protein could enhance oncolytic HAdV efficacy and reduce tumor growth rate in a human xenograft mouse model of cancer. We now explore whether co-expression of the adenovirus death protein (ADP) with p14 FAST protein could synergize to further enhance oncolytic vector efficacy. ADP is naturally encoded within the early region 3 (E3) of HAdV, a region which is frequently removed from HAdV-based vectors, and functions to enhance cell lysis and progeny release. We evaluated a variety of approaches to achieve optimal expression of the two proteins, the most efficient method being insertion of an expression cassette within the E3 deletion, consisting of the coding sequences for p14 FAST protein and ADP separated by a self-cleaving peptide derived from the porcine teschovirus-1 (P2A). However, the quantities of p14 FAST protein and ADP produced from this vector were reduced approximately 10-fold compared to a similar vector-expressing only p14 FAST protein and wildtype HAdV, respectively. Compared to our original oncolytic vector-expressing p14 FAST protein alone, reduced expression of p14 FAST protein and ADP from the P2A construct reduced cell-cell fusion, vector spread, and cell-killing activity in human A549 adenocarcinoma cells in culture. These studies show that a self-cleaving peptide can be used to express two different transgenes in an armed oncolytic HAdV vector, but also highlight the challenges in maintaining adequate transgene expression when modifying vector design.

Convergent neural signatures of speech prediction error are a biological marker for spoken word recognition

We use MEG and fMRI to determine how predictions are combined with speech input in superior temporal cortex. We compare neural responses to words in which first syllables strongly or weakly predict second syllables (e.g., “bingo”, “snigger” versus “tango”, “meagre”). We further compare neural responses to the same second syllables when predictions mismatch with input during pseudoword perception (e.g., “snigo” and “meago”). Neural representations of second syllables are suppressed by strong predictions when predictions match sensory input but show the opposite effect when predictions mismatch. Computational simulations show that this interaction is consistent with prediction error but not alternative (sharpened signal) computations. Neural signatures of prediction error are observed 200 ms after second syllable onset and in early auditory regions (bilateral Heschl’s gyrus and STG). These findings demonstrate prediction error computations during the identification of familiar spoken words and perception of unfamiliar pseudowords.

MRI-free processing of tau PET images for early detection

Abstract Tau positron emission tomography (PET) imaging in Alzheimer’s Disease (AD) is becoming increasingly common to assess in vivo tau burden. MR images are often acquired to assist with processing of PET data, including for region-of-interest definitions in native space and for normalization to template space. However, in the real-world setting, corresponding MRIs may not be available and PET processing may require MRI-free pipelines. This is particularly important and challenging as the field moves towards early detection among clinically unimpaired (CU) individuals where changes in tau PET signal are expected to be subtle. We used two independent [18F]Flortaucipir tau PET datasets to evaluate whether MRI-free PET processing can detect subtle tau PET uptake differences in Amyloid+ (A+) CU individuals (preclinical AD) versus A-. Standardized Uptake Value Ratios (SUVRs) from MRI-free compared to MRI-based methods were evaluated using linear regression and linear mixed-effects regression models. Effect size differences between A+/- CU groups in MRI-free processed cross-sectional and longitudinal tau PET SUVRs were compared to differences quantified through MRI-based processing. Regional MRI-free SUVRs were highly correlated with MRI-based SUVRs within CU individuals (average ICC = 0.90 for ADNI CU and 0.81 for A4 CU). MRI-free and MRI-based pipelines resulted in similar estimates of cross-sectional and longitudinal differences between A- and A+ CU, even in early focal regions within the medial temporal lobe.

Single-cell RNA-sequencing of BK polyomavirus replication in primary human renal proximal tubular epithelial cells identifies specific transcriptome signatures and a novel mitochondrial stress pattern.

BK polyomavirus (BKPyV) contributes to premature renal failure in 10%-20% of kidney transplant recipients. Current treatment relies on reducing immunosuppression to regain BKPyV-specific immune control. Subsequently, declining allograft function may result from persisting viral cytopathology, BKPyV-specific immune reconstitution, or alloimmunity/rejection, all being poorly distinguishable by current histological or molecular approaches. To reduce the complexity encountered in BKPyV-replicating kidneys, we analyzed differentially expressed genes (DEGs) in primary human renal proximal tubular epithelial cells at 24 and 48 h post-infection (hpi) using single-cell RNA-sequencing (10x-Genomics-3´ kit). At 24 hpi, viral transcript reads predominantly mapped to the early viral gene region (EVGR) and shifted to >100-fold higher late viral gene region (LVGR) levels at 48 hpi, matching the sequential bi-directional viral protein expression from the circular double-stranded BKPyV-DNA genome. Besides expected coverage "hills" at viral 3´-poly-A sites, unexpected "spike" and "pulse" reads resulted from off-target TSO priming. "Spike" and "pulse" patterns were rare for the mostly unidirectional reads mapping to the circular mitochondrial genome. Bioinformatic curation removed "spikes" and "pulses" and reclassified 10% of DEGs in renal proximal tubular epithelial cells (RPTECs). Up-regulated gene ontologies included S and G2/M phase, double-stranded DNA repair, proximal tubulopathy, and renal tubular dysfunction, whereas allograft rejection, antigen presentation, innate immunity, translation, and autophagy were down-regulated. BKPyV-LVGR expression induced a novel mitochondrial cell stress pattern consisting of discordant up-regulation and down-regulation of mitochondria-encoded and nucleus-encoded mitochondrial genes, respectively. We explored which top-scoring gene sets of late-phase BKPyV-replicating RPTECs can identify BKPyV-associated nephropathy in kidney transplant biopsies. The results should facilitate distinguishing BKPyV-associated pathology from other entities in kidney transplant biopsies.IMPORTANCEBK polyomavirus (BKPyV) infects more than 90% of the general population and then persists in the reno-urinary tract. Subsequently, low-level urinary shedding is seen in 10% of healthy BKPyV-seropositive persons, indicating that BKPyV replication occurs despite the presence of virus-specific cellular and humoral immunity. Notably, transplantation of donor kidneys with low-level BKPyV replication is a risk factor for progression to high-level BKPyV viruria, new-onset BKPyV-DNAemia and biopsy-proven BKPyV nephropathy. Here, we identify a short list of robust up- and down-regulated nucleus-encoded differentially expressed genes potentially allowing to discriminate viral from allograft immune damage. By carefully curating viral and mitochondrial transcriptomes, we identify a novel virus-associated mitochondrial stress pattern of up-regulated mitochondria-encoded and down-regulated nucleus-encoded mitochondrial transcripts which heralds the BKPyV-agnoprotein-mediated immune escape by breakdown of the mitochondrial membrane potential and network and mitophagy. The results may prove useful when assessing the role of BKPyV replication in kidney transplant patients with suspected acute rejection and/or BKPyV nephropathy.

Longitudinal relationships between Aβ and tau to executive function and memory in cognitively normal older adults

The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an “Aβ-executive function, tau-memory” double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere. The activations in the face and object processing ventrolateral visual cortical stream regions FFC, PIT, V8 and TE2p were higher in the object-location in scene task than the reward-location task, and were higher in the right hemisphere. For reward-location in scene episodic memory, activations were also high in the ventromedial visual cortical spatial stream to the hippocampus, but were also selectively high in storage in key reward cortical regions (ventromedial prefrontal 10r, 10v, 10d; pregenual anterior cingulate d32, p24, p32, s32; and medial orbitofrontal cortex reward-related pOFC, 11l, OFC). For word-pair episodic memory, activations were lower in the ventromedial visual and medial parahippocampal spatial cortical stream, and were higher in language-related regions in Broca's area (44, 45, 47l), and were higher in the left hemisphere for these regions and for the many highly connected inferior frontal gyrus regions in the left hemisphere. Further, effective connectivity analyses during the episodic memory tasks showed that the direction of connectivity for these systems was from early visual cortical regions V2-V4 to the ventromedial visual cortical regions VMV1-3 and VVC for spatial scene processing; was from the pregenual anterior cingulate and orbitofrontal cortex reward systems to the hippocampal system; and was from the FFC/V8/PIT system to TE2p in the visual inferior temporal visual cortex, which has connectivity to lateral parahippocampal TF, which in turn has forward effective connectivity to the hippocampus.

Spatiotemporal topology of religious spread in a multi‐religious metropolis: A historical religious profile of Taipei City in Taiwan from 1660 to 2020

AbstractReligious identities play an important role in shaping migrants' experiences. Understanding the spatiotemporal distribution of religions enhances our knowledge of both religious expansion and religious cultures. This paper aims to leverage spatiotemporal analysis to characterise the topology of the spread of multiple religions in the Taipei metropolitan area from 1660 to 2020, including Folk Taoism (853 temples/altars, 55.39%), Christianity (306 churches, 19.87%) and Buddhism (332 temples, 21.56%). Three major factors affecting religious distribution are considered: the year of establishment of religious units (churches, temples or altars), the reclamation year of religious locations, and the economic index of religious sites. The results show that Folk Taoism and Buddhism have a long history of development in early reclamation regions with a hopping expansion pattern. However, Christianity expanded later in the later reclaimed and early reclaimed areas. The Christian religious units have highly concentrated spatial patterns and are located in the higher‐income districts, centralised in the core regions of the Taipei metropolis. Modern forms of highly institutionalised religion, such as Buddhism and Christianity, are more prevalent in the relatively higher‐income, later‐cultivated areas, which provide richer social resources for development. Folk Taoism, as a traditional religion, is maintained and developed by local communities. This macroscopic analysis helps to (1) identify the exact chronology of different growth waves and explain them in a historical context, and (2) elucidate the spatial distribution differences between institutionalised religions and folk religion. Our research shows the evolution of religious landscapes from an undeveloped city to a developed city, offering valuable insights for geographical and religious studies, and enhancing understanding of diffused and institutionalised religious expansion.

Multiphase Tectonic Processes in the Mesozoic and Formation of Early Regional Geomorphic Pattern in the Qilian Orogenic Belt, Northeastern Tibetan Plateau

Abstract Conventional orogenic settings are largely confined to plate boundaries and their immediate vicinity. However, there is growing recognition that deformation of the continental lithosphere may extend for considerable distances away from active plate boundaries. The Mesozoic Qilian orogenic belt occupies a key position in East Asia and thus is important to consider when interpreting intracontinental deformation there. To determine when and how the North Qilian orogenic belt developed, multiple sets of samples collected from the Dahuang Mountain of the North Qilian orogenic belt were analyzed for apatite (U-Th)/He and zircon (U-Th)/He thermochronology. The results show that the study area experienced multiphase tectonic exhumation events that took place in the Early-Middle Triassic (250–235 Ma), Middle-Late Jurassic (170–150 Ma), and Early Cretaceous (130–110 Ma). This study reveals that the generation deformation and stress distribution in the Dahuang Mountain fold-fault system have the characteristics of temporal–spatial migration from N to S. Results indicate widespread, continuous exhumation and deposition in the Qilian Mountain due to multiplate interaction since the Mesozoic, persisting till at least late Miocene. Multiphase intracontinental deformation is driven by stresses at plate boundaries, with lithosphere serving as stress pathway.

Manipulating attentional priority creates a trade-off between memory and sensory representations in human visual cortex.

People often remember visual information over brief delays while actively engaging with ongoing inputs from the surrounding visual environment. Depending on the situation, one might prioritize mnemonic contents (i.e., remembering details of a past event), or preferentially attend sensory inputs (i.e., minding traffic while crossing a street). Previous fMRI work has shown that early sensory regions can simultaneously represent both mnemonic and passively viewed sensory information. Here we test the limits of such simultaneity by manipulating attention towards sensory distractors during a working memory task performed by human subjects during fMRI scanning. Participants remembered the orientation of a target grating while a distractor grating was shown during the middle portion of the memory delay. Critically, there were several subtle changes in the contrast and the orientation of the distractor, and participants were cued to either ignore the distractor, detect a change in contrast, or detect a change in orientation. Despite sensory stimulation being matched in all three conditions, the fidelity of memory representations in early visual cortex was highest when the distractor was ignored, intermediate when participants attended distractor contrast, and lowest when participants attended the orientation of the distractor during the delay. In contrast, the fidelity of distractor representations was lowest when ignoring the distractor, intermediate when attending distractor-contrast, and highest when attending distractor-orientation. These data suggest a trade-off in early sensory representations when engaging top-down feedback to attend both seen and remembered features and may partially explain memory failures that occur when subjects are distracted by external events.

Identification of the Potential Role of the E4orf4 Protein in Adenovirus A, B, C, and D Groups in Cancer Therapy: Computational Approaches.

The human adenovirus (HADV) early region 4 open reading frame 4 (E4orf4) protein plays a regulatory role in promoting viral infection by interacting with various cellular proteins. E4orf4 can induce death in cancer cells. One of the death pathways that is induced by this protein is related to the formation of membrane blebbing following the phosphorylation of tyrosine amino acids. The activation of this pathway requires the interaction of E4orf4 with Src family kinases (SFKs). The modulation mechanism of Src-dependent signaling via E4orf4 is not yet fully understood. However, evidence suggests that a physical association between the Src kinase domain and the arginine-rich motif of E4orf4 is crucial. Physically connecting E4orf4 to Src kinase leads to the deregulation of the Src-related signaling pathway, thereby inducing cytoplasmic death. In this study, we mapped the E4orf4 interaction site in Src to investigate the interaction between E4orf4 and Src in detail. We also compared the binding strength of E4orf4 proteins from different HADV groups. To this end, we performed bioinformatics structural analysis of the Src kinase domain and E4orf4 to identify E4orf4 interaction sites. The group with the lowest binding energy was predicted to be the most likely candidate for the highest cytoplasmic death in tumor cells based on the energy of the E4orf4-Src complex in various HADV groups. These results show that HADV-A and HADV-C have minimal binding energies to the E4orf4-Src complex, while the dissociation constant (Kd) of HADV-A was less than that of HADV-C. According to the obtained results, E4orf4 of the HADV-A group is more effective at triggering cytoplasmic death based on its most robust interaction with the Src kinase domain.

Task-specific invariant representation in auditory cortex.

Categorical sensory representations are critical for many behaviors, including speech perception. In the auditory system, categorical information is thought to arise hierarchically, becoming increasingly prominent in higher-order cortical regions. The neural mechanisms that support this robust and flexible computation remain poorly understood. Here, we studied sound representations in the ferret primary and non-primary auditory cortex while animals engaged in a challenging sound discrimination task. Population-level decoding of simultaneously recorded single neurons revealed that task engagement caused categorical sound representations to emerge in non-primary auditory cortex. In primary auditory cortex, task engagement caused a general enhancement of sound decoding that was not specific to task-relevant categories. These findings are consistent with mixed selectivity models of neural disentanglement, in which early sensory regions build an overcomplete representation of the world and allow neurons in downstream brain regions to flexibly and selectively read out behaviorally relevant, categorical information.

Diversity of Shiga toxin transducing phages in Escherichia coli O145:H28 and the different Shiga toxin 2 production levels associated with short- or long-tailed phages.

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes serious gastrointestinal illness, including hemorrhagic colitis and hemolytic uremic syndrome. Two types of Stxs (Stx1 and Stx2) are known and both are encoded by bacteriophages (Stx phages), but the production of Stx2 is known to be a major risk factor for severe STEC infections. The production of Stx2, but not Stx1, is tightly coupled with the induction of Stx phages, and Stx2 production levels vary between STEC strains even within the same serotype. Here, we analyzed the genomic diversity of all Stx phages in 71 strains representing the entire O145:H28 lineage, one of the often highly pathogenic STECs, and the relationship between the variations in Stx phage genomes and the levels of Stx2 production by host strains. Our analysis reveals highly dynamic natures of Stx phages in O145:H28, including the independent acquisition of similar Stx phages by different sublineages, the recent transfer of Stx phage between different sublineages, and the frequent gain and loss of Stx phages in some sublineages. We also show the association of the Stx2 phage types with the Stx2 production levels of host strains: strains carrying short-tailed Stx2 phages exhibited significantly higher Stx2 production levels than those carrying long-tailed Stx2 phages. Detailed analyses of the Stx2 phage genomes revealed that both of short- and long-tailed phages exhibited sequence diversification and they were divided into two groups, respectively, based on the sequence similarity of the phage early region encoding genes responsible for phage induction, short-tailed phages contained early regions clearly different in genetic organization from those in long-tailed phages. Therefore, the variations in the early regions between short-and long-tailed Stx2 phages appeared to be linked to a striking difference in Stx2 production levels in their host strains. These results broaden our understanding of the diversification and dynamism of Stx phages in O145:H28 and the association of Stx2 phage types with the Stx2 production level in this STEC lineage.

Selective Attention and Decision-Making Have Separable Neural Bases in Space and Time.

Attention and decision-making processes are fundamental to cognition. However, they are usually experimentally confounded, making it difficult to link neural observations to specific processes. Here we separated the effects of selective attention from the effects of decision-making on brain activity obtained from human participants (both sexes), using a two-stage task where the attended stimulus and decision were orthogonal and separated in time. Multivariate pattern analyses of multimodal neuroimaging data revealed the dynamics of perceptual and decision-related information coding through time with magnetoencephalography (MEG), through space with functional magnetic resonance imaging (fMRI), and their combination (MEG-fMRI fusion). Our MEG results showed an effect of attention before decision-making could begin, and fMRI results showed an attention effect in early visual and frontoparietal regions. Model-based MEG-fMRI fusion suggested that attention boosted stimulus information in the frontoparietal and early visual regions before decision-making was possible. Together, our results suggest that attention affects neural stimulus representations in the frontoparietal regions independent of decision-making.

Bone Turnover Markers and Wnt Signaling Modulators in Early Complex Regional Pain Syndrome. A Pre-specified Observational Study.

To explore serum levels of some bone turnover markers and the involvement of the Wnt signaling in CRPS-1. Query ID="Q1" Text="Please check and confirm whether the edit made to the article title is in order." We conducted an observational study on patients with early CRPS-1 recruited before any treatment. Clinical measures were assessed together with biochemical evaluation. Values of sclerostin, DKK1, CTX-I, and P1NP were compared with sex-age-matched healthy controls (HCs). We enrolled 34 patients diagnosed with CRPS-1 (mean age 59.3 ± 10.6years, Male/Female 10/24), median disease duration = 2weeks (IQR 1-5); median VAS score = 76 (IQR 68-80). Foot localization was slightly more frequent than hand localization (18/16). No statistically significant difference was found between CRPS-1 patients and HCs for CTX-I (0.3 ± 0.1ng/ml vs 0.3 ± 0.1, p = 0.140), while mean serum values of P1NP were significantly higher in CRPS-1 patients compared to HCs (70.0 ± 38.8ng/ml vs 50.1 ± 13.6, p = 0.005). Mean levels of sclerostin and DKK1 were lower in CRPS-1 patients vs HCs (sclerostin 28.4 ± 10.8pmol/l vs 34.1 ± 11.6, p = 0.004; DKK1 12.9 ± 10.8pmol/l vs 24.1 ± 11.9, p = 0.001). No statistically significant difference was found for all biochemical assessments in a subgroup of fracture-induced CRPS-1. No statistically significant differences were observed according to disease localization, disease duration, presence of hyperalgesia, allodynia, sudomotor alterations, and mild or moderate/severe swelling. No significant correlation emerged between sclerostin, DKK1 levels, baseline VAS score, or McGill Pain Questionnaire score. Bone involvement in early CRPS-1 does not seem to rely on increased osteoclast activity. Conversely, a serum marker of bone formation resulted increased. Both Sclerostin and DKK1 showed decreased values, probably suggesting a widespread osteocyte loss of function.Trial registration number: Eudract Number: 2014-001156-28.

Improving acute stroke assessment in non-enhanced computed tomography: automated tool for early ischemic lesion volume detection.

ASPECTs is a widely used marker to identify early stroke signs on non-enhanced computed tomography (NECT), yet it presents interindividual variability and it may be hard to use for non-experts. We introduce an algorithm capable of automatically estimating the NECT volumetric extension of early acute ischemic changes in the 3D space. We compared the power of this marker with ASPECTs evaluated by experienced practitioner in predicting the clinical outcome. We analyzed and processed neuroimaging data of 153 patients admitted with acute ischemic stroke. All patients underwent a NECT at admission and on follow-up. The developed algorithm identifies the early ischemic hypodense region based on an automatic comparison of the gray level in the images of the two hemispheres, assumed to be an approximate mirror image of each other in healthy patients. In the two standard axial slices used to estimate the ASPECTs, the regions identified by the algorithm overlap significantly with those identified by experienced practitioners. However, in many patients, the regions identified automatically extend significantly to other slices. In these cases,the volume marker provides supplementary and independent information.Indeed,theclinical outcome of patients with volume marker = 0 can be distinguished with higher statistical confidence than the outcome of patients with ASPECTs = 10. The volumetric extension and the location of acute ischemic region in the 3D-space, automatically identified by our algorithm, provide data that are mostly in agreement with the ASPECTs value estimated by expert practitioners, and in some cases complementary and independent.

공렬토기의 기원과 편년에 대한 학사적 검토

In this article, the research history of the origin and chronology of rim-perforated pottery since the 1960s was reviewed to examine the changes in perception and research trends of origin, typology, and chronology in the study of the Bronze Age. rim-perforated pottery was recognized as an earthenware with cultural continuity that appeared from the end of the Neolithic Age as it was exported together with the comb-pattern earthenware from the ruins of Hogok-dong, Musan. Under this background, rim-perforated pottery in the 60s and 80s has been treated as a material culture representing the early Bronze Age along with Garakdong-style earthenware. Then, after the 90s, as a number of large-scale settlement sites of the Bronze Age were investigated, data from the early period, including stone gate earthenware, were accumulated. For this reason, different views on the origin and timing of the emergence of rim-perforated pottery began to be presented. Regarding the lower limit date of rim-perforated pottery, researchers tend to space between researchers, but the aspects of material data in the early South Korean region, such as stone gate earthenware, square earthenware, double-headed earthenware, etc., are different, so there is not a small difference of opinion among researchers on the genealogy, chronology, and development process of Gongryeol earthenware surrounding it. The proposal of cultural types has great academic significance in discussing the development process of the Mumun pottery era in South Korea. The cultural type is the result of organizing material culture and putting it in a certain time and space, and is also understood as a branch itself. As for the initially proposed cultural type, the contents continued to be changed, subdivided, and inclusive as data were added so far. As Rim-Perforated Pottery was also established as an Yeoksam-dong type, it underwent changes in many parts of the origin and chronology. Since the cultural type is a series of material complexes completed by itself, it has a problem that it is difficult to grasp the layered and dynamic aspects of the data under this concept. In order for the discussion on rim-perforated pottery to proceed, it is not necessary to grasp it as an element of the completed cultural type earthenware from the beginning, but to deal with the entire process of being established as an Yeoksam-dong type in the earthenware at the first sight. Only at this time will we be able to examine the temporal location of rim-perforated pottery, regional variations, and the usefulness of the devised Yeoksam-dong type.

Formation of N–bearing complex organic molecules in molecular clouds: Ketenimine, acetonitrile, acetaldimine, and vinylamine via the UV photolysis of C2H2 ice

Context. The solid-state C2H2 chemistry in interstellar H2O-rich ice has been proposed to explain astronomically observed complex organic molecules (COMs), including ketene (CH2CO), acetaldehyde (CH3CHO), and ethanol (CH3CH2OH), toward early star-forming regions. This formation mechanism is supported by recent laboratory studies and theoretical calculations for the reactions of C2H2+OH/H. However, the analog reaction of C2H2+NH2 forming N-bearing species has been suggested to have a relatively low rate constant that is orders of magnitude lower than the value of C2H2+OH. Aims. This work extends our previous laboratory studies on O-bearing COM formation to investigate the interactions between C2H2 and NH3 ice triggered by cosmic ray-induced secondary UV photons under molecular cloud conditions. Methods. Experiments were performed in an ultra-high vacuum chamber to investigate the UV photolysis of the C2H2:NH3 ice mixture at 10 K. The ongoing chemistry was monitored in situ by Fourier-transform infrared spectroscopy as a function of photon fluence. The IR spectral identification of the newly formed N-bearing products was further secured by a quadrupole mass spectrometer during the temperature-programmed desorption experiment. Results. The studied ice chemistry of C2 H2 with NH2 radicals and H atoms resulting from the UV photodissociation of NH3 leads to the formation of several N-bearing COMs, including vinylamine (CH2CHNH2), acetaldimine (CH3CHNH), acetonitrile (CH3CN), ketenimine (CH2CNH), and tentatively ethylamine (CH3CH2NH2). The experimental results show an immediate and abundant CH2CHNH2 yield as the first-generation product, which is further converted into other chemical derivatives. The effective destruction and formation cross-section values of parent species and COMs were derived, and we discuss the chemical links among these molecules and their astronomical relevance.

HPV8-induced STAT3 activation led keratinocyte stem cell expansion in human actinic keratoses.

Despite epidermal turnover, the skin is host to a complex array of microbes, including viruses, such as HPV, which must infect and manipulate skin keratinocyte stem cells (KSCs) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+ hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+ KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induced ΔNp63 expression, resulting in KSC expansion into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses. Together, these results define the "hit-and-run" mechanism for HPV8 in human actinic keratosis as an expansion of KSCs, which lack melanosome protection and are thus susceptible to sun light-induced malignant transformation.