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Somatostatin receptors (SSTRs) are widely distributed throughout the human body and play crucial roles in various physiological processes. They are recognized as key targets for both radiotherapy and radiodiagnosis due to their overexpression in several cancer types. However, the discovery and design of selective drugs for each of the five isoforms have been significantly hindered by the lack of complete structural information. In this study, we conducted a systematic computational analysis of all five SSTRs in complex with the endogenous ligand somatostatin to elucidate their structural and dynamic features. We thoroughly characterized each isoform using available experimental structures for SSTR2 and SSTR4, as well as AlphaFold2 models for SSTR1, SSTR3, and SSTR5. By performing multi-copy μs-long molecular dynamics simulations, we examined the differences and similarities in dynamical behavior and somatostatin binding among all SSTRs. Our analysis focused on understanding the opening and closing movements of the extracellular loop 2, which are crucial for ligand binding and recognition. Interestingly, we observed a unique conformation of somatostatin within the binding pocket of SSTR5 in which the loop can partially close, as compared to the other isoforms. Fingerprint analyses provided distinct interaction patterns of somatostatin with all receptors, thus enabling precise guidelines for the discovery and development of more selective somatostatin-based pharmaceuticals tailored for precision medicine therapies.

Abstract The recent colder winters in midlatitude Eurasia have been proposed to result from Arctic sea-ice decline. However, large uncertainties remain regarding this link in the present variable climate. Here, we present ice-rafted debris records from the eastern Arctic and geochemical data from the temperate East China Sea to reconstruct Holocene changes in sea ice and the East Asian winter monsoon. Our reconstructions and climate numerical simulations revealed enhanced Arctic sea-ice decline but warmer winters in East Asia in the mid-Holocene than in the late Holocene. In the warmer mid-Holocene, enhanced Arctic sea-ice loss transferred more heat from intensive summer solar insolation to the winter atmosphere, suppressing meridional heat transport; thus, less high-latitude cold air moved to lower latitudes in Asia due to the weakened winter monsoon. Our findings imply that the colder winters in East Asia may not change the long-term trend toward winter warming in the context of Arctic sea-ice decline.

Numerous studies, spanning experimental, instrumental, historical, and modeled approaches, have delved into understanding climate change across the Holocene era and millennial-scale occurrences. However, the chronology and causes of centennial-scale climate events during the Holocene remain controversial. In this study, we overviewed 10 of the best-resolved and most accurately dated records detailing climate change in the Northern Hemisphere (NH) over the Holocene, obtained from different proxies across different climatic zones, and constructed a stack of temperature changes in the NH. Based on the constructed stack, we identified and categorized 15 notable Holocene centennial cooling events (HCCEs) in the NH (period with temperature decreases). To test the chronological validity of the constructed HCCEs, we compared them with the most accurately dated and highly resolved climate records during the last 3 kyr, which have been extensively investigated by the scientific community. Based on the close alignment of the outlined HCCEs with temperature records, we suggest that other HCCEs also match centennial climate cooling events over the last 10 kyr. To understand the origins of the established HCCEs, we compared them with potential climate influencing factors: total solar irradiance (TSI), explosive volcanic activity, Atlantic meridional overturning circulation (AMOC)-limited slowdowns, Intertropical Convergence Zone (ITCZ) fluctuations, and El Niño/Southern Oscillation (ENSO variability. Early Holocene HCCE 5, terminated by a prominent 8.2-ka cold event, was likely driven by the superposition of the AMOC limited slowdown, TSI minimum, and volcanic activity. The Holocene Thermal Maximum (HTM) happened between HCCEs 5 and 4a and was interrupted by HCCE 4c and 4b, coeval, with a significant southward shift of the ITCZ, likely related to cooling in the tropical zone. However, the sequence of HCCEs 3b, 3a, and 2b (over 4.53–3.42 BP), accompanied by small changes in the TSI, was likely forced by an increase in ENSO variability, leading to remarkable changes in the tropical processes and a southward shift of the ITCZ, coeval with the collapse of the Chinese Neolithic cultures and onset of the Holocene Neoglacial. Subsequent HCCEs 2a–0a were likely forced by the TSI minimum combined with the influence of ENSO and volcanism over the last 2 ka.

Abstract The polar oceans play a vital role in regulating atmospheric CO2 concentrations (pCO2) during the Pleistocene glacial cycles. However, despite being the largest modern reservoir of respired carbon, the impact of the subarctic Pacific remains poorly understood due to limited records. Here, we present high-resolution, 230Th-normalized export productivity records from the subarctic northwestern Pacific covering the last five glacial cycles. Our records display pronounced, glacial-interglacial cyclicity superimposed with precessional-driven variability, with warm interglacial climate and high boreal summer insolation providing favorable conditions to sustain upwelling of nutrient-rich subsurface waters and hence increased export productivity. Our transient model simulations consistently show that ice sheets and to a lesser degree, precession are the main drivers that control the strength and latitudinal position of the westerlies. Enhanced upwelling of nutrient/carbon-rich water caused by the intensification and poleward migration of the northern westerlies during warmer climate intervals would have led to the release of previously sequestered CO2 from the subarctic Pacific to the atmosphere. Our results also highlight the significant role of the subarctic Pacific in modulating pCO2 changes during the Pleistocene climate cycles, especially on precession timescale ( ~ 20 kyr).

Radiopharmaceuticals are currently a key tool in cancer diagnosis and therapy. Metal-based radiopharmaceuticals are characterized by a radiometal–chelator moiety linked to a bio-vector that binds the biological target (e.g., a protein overexpressed in a particular tumor). The right match between radiometal and chelator influences the stability of the complex and the drug’s efficacy. Therefore, the coupling of the radioactive element to the correct chelator requires consideration of several features of the radiometal, such as its oxidation state, ionic radius, and coordination geometry. In this work, we systematically investigated about 120 radiometal–chelator complexes taken from the Cambridge Structural Database. We considered 25 radiometals and about 30 chelators, featuring both cyclic and acyclic geometries. We used quantum mechanics methods at the density functional theoretical level to generate the general AMBER force field parameters and to perform 1 µs-long all-atom molecular dynamics simulations in explicit water solution. From these calculations, we extracted several key molecular descriptors accounting for both electronic- and dynamical-based properties. The whole workflow was carefully validated, and selected test-cases were investigated in detail. Molecular descriptors and force field parameters for the complexes considered in this study are made freely available, thus enabling their use in predictive models, molecular modelling, and molecular dynamics investigations of the interaction of compounds with macromolecular targets. Our work provides new insights in understanding the properties of radiometal–chelator complexes, with a direct impact for rational drug design of this important class of drugs.

BACKGROUND: The DutchBelgian Randomized Lung Cancer Screening Trial (NELSON) used a volume-based protocol and significantly reduced the prevalence of false-positive results (2.1%). AIM: To compare the performance of manual linear diameter and semi-automated volumetric nodule measurement in the pilot project Moscow Lung Cancer Screening ultra-low-dose computed tomography pilot study. MATERIALS AND METHODS: The study included individuals with a lung nodule of at least 4 mm on baseline-computed tomography of the Moscow lung cancer screening between February 2017 and February 2018, without verified lung cancer diagnosis until 2020. The radiation dose was selected individually and did not exceed 1 mSv. All scans were assessed by three blinded readers to measure the maximum and minimum transversal nodule diameter and extrapolated volume. As a reference value of size and volume, the average value from the results of expert measurements was obtained. A false-positive nodule was defined as a nodule 6 mm/100 mm3 and a false-negative nodule as a nodule 6 mm/100 mm3. RESULTS: Overall, 293 patients were included (166 men; mean age, 64.6 5.3years); 199 lung nodules were 6 mm/100 mm3 and 94 were 6 mm/100 mm3. Regarding volumetric measurements, 32 [10.9%; 4 false-positive, 28 false-negative], 29 [9.9%; 17 false-positive, 12 false-negative], and 30 [10.2%; 6 false-positive, 24 false-negative] nodule discrepancies were reported by readers 1, 2, and 3 respectively. For linear diameter measurement, 92 [65.5%; 107 false-positive, 85 false-negative], 146 [49.8%; 58 false-positive, 88 false-negative], and 102 [34.8%; 23 false-positive, 79 false-negative] nodule discrepancies were reported by readers 1, 2, and 3 respectively. CONCLUSIONS: The use of lung nodule volumetry strongly reduces the number of false-positive and false-negative nodules compared with nodule diameter measurements, in an ultra-low-dose computed tomography lung cancer screening program.

In the article "Volumetry versus linear diameter lung nodule measurement: an ultra-low-dose computed tomography lung cancer screening study" published in Digital Diagnostics journal Volume 4 Issue 1 in 2023 (doi: 10.17816/DD117481) contained an error in the paragraph with data of funding sources for the study. At the request of the authors team, the error was eliminated, the original version of the published article and the information on the journals site was replaced with the corrected one. Correct text of the changed: This paper was prepared by a group of authors as part of the research work (USIS No. 123031400009-1) in accordance with the Order issued by the Moscow Health Care Department No. 1196 dated December 21, 2022. The authors and the publisher apologize to readers for the published error and express their confidence that this mistake could not significantly affect the perception and interpretation of the results of the study described in the text of the article.

Abstract The cyclic peptide hormone somatostatin regulates physiological processes involved in growth and metabolism, through its binding to G-protein coupled somatostatin receptors. The isoform 2 (SSTR2) is of particular relevance for the therapy of neuroendocrine tumours for which different analogues to somatostatin are currently in clinical use. We present an extensive and systematic computational study on the dynamics of SSTR2 in three different states: active agonist-bound, inactive antagonist-bound and apo inactive. We exploited the recent burst of SSTR2 experimental structures to perform μs-long multi-copy molecular dynamics simulations to sample conformational changes of the receptor and rationalize its binding to different ligands (the agonists somatostatin and octreotide, and the antagonist CYN154806). Our findings suggest that the apo form is more flexible compared to the holo ones, and confirm that the extracellular loop 2 closes upon the agonist octreotide but not upon the antagonist CYN154806. Based on interaction fingerprint analyses and free energy calculations, we found that all peptides similarly interact with residues buried into the binding pocket. Conversely, specific patterns of interactions are found with residues located in the external portion of the pocket, at the basis of the extracellular loops, particularly distinguishing the agonists from the antagonist. This study will help in the design of new somatostatin-based compounds for theranostics of neuroendocrine tumours.

Objective: Bi-allelic loss-of-function mutations in TSHB, encoding the beta subunit of thyroid-stimulating hormone (TSH), cause congenital hypothyroidism. Homozygosity for the TSHB p.R75G variant, previously described in South Asian individuals, does not alter TSH function but abrogates its detection by some immune detection-based platforms, leading to erroneous diagnosis of hyperthyroidism. We set out to identify and determine the carrier rate of the p.R75G variant among clinically euthyroid Bene Israel Indian Jews, to examine the possible founder origin of this variant worldwide, and to determine the phenotypic effects of its heterozygosity. Design: Molecular genetic studies of Bene Israel Jews and comparative studies with South Asian cohort. Methods: TSHB p.R75G variant tested by Sanger sequencing and restriction fragment length polymorphism (RFLP). Haplotype analysis in the vicinity of the TSHB gene performed using SNP arrays. Results: Clinically euthyroid individuals with low or undetectable TSH levels from three apparently unrelated Israeli Jewish families of Bene Israel ethnicity, originating from the Mumbai region of India, were found heterozygous or homozygous for the p.R75G TSHB variant. Extremely high carrier rate of p.R75G TSHB in Bene Israel Indian Jews (~4%) was observed. A haplotype block of 239.7 kB in the vicinity of TSHB shared by Bene Israel and individuals of South Asian origin was detected. Conclusions: Our findings highlight the high prevalence of the R75G TSHB var iant in euthyroid Bene Israel Indian Jews, demonstrate that heterozygosity of this variant can cause erroneous detection of subnormal TSH levels, and show that R75G TSHB is an ancient founder variant, delineating shared ancestry of its carriers.

ABSTRACT Transporters of the resistance-nodulation-cell division (RND) superfamily of proteins are the dominant multidrug efflux power of Gram-negative bacteria. The major RND efflux pump of Pseudomonas aeruginosa is MexAB-OprM, in which the inner membrane transporter MexB is responsible for the recognition and binding of compounds. The high importance of this pump in clinical antibiotic resistance made it a subject of intense investigations and a promising target for the discovery of efflux pump inhibitors. This study is focused on a series of peptidomimetic compounds developed as effective inhibitors of MexAB-OprM. We performed multi-copy molecular dynamics simulations, machine-learning (ML) analyses, and site-directed mutagenesis of MexB to investigate interactions of MexB with representatives of efflux avoiders, substrates, and inhibitors. The analysis of both direct and water-mediated protein-ligand interactions revealed characteristic patterns for each class, highlighting significant differences between them. We found that efflux avoiders poorly interact with the access binding site of MexB, and inhibition engages amino acid residues that are not directly involved in binding and transport of substrates. In agreement, machine-learning models selected different residues predictive of MexB substrates and inhibitors. The differences in interactions were further validated by site-directed mutagenesis. We conclude that the substrate translocation and inhibition pathways of MexB split at the interface (between the main putative binding sites) and at the deep binding pocket and that interactions outside of the hydrophobic patch contribute to the inhibition of MexB. This molecular-level information could help in the rational design of new inhibitors and antibiotics less susceptible to the efflux mechanism. IMPORTANCE Multidrug transporters recognize and expel from cells a broad range of ligands including their own inhibitors. The difference between the substrate translocation and inhibition routes remains unclear. In this study, machine learning and computational and experimental approaches were used to understand dynamics of MexB interactions with its ligands. Our results show that some ligands engage a certain combination of polar and charged residues in MexB binding sites to be effectively expelled into the exit funnel, whereas others engage aromatic and hydrophobic residues that slow down or hinder the next step in the transporter cycle. These findings suggest that all MexB ligands fit into this substrate-inhibitor spectrum depending on their physico-chemical structures and properties.

Based on marine multiproxy records, a new study outlines the role of larger heat discharge of the pan-Arctic Rivers in determining the pronounced sea ice retreat over the East Siberian Arctic Shelf in the mid-Holocene.

Measurement(s) molecular physical property analysis objective Technology Type(s) Computer Modeling

Numerous studies, spanning experimental, instrumental, historical, and modeled approaches, have delved into understanding climate change across the Holocene era and millennial-scale occurrences. However, the chronology and causes of centennial-scale climate events during the Holocene remain controversial. In this study, we overviewed 10 of the best-resolved and most accurately dated records detailing climate change in the Northern Hemisphere (NH) over the Holocene, obtained from different proxies across different climatic zones, and constructed a stack of temperature changes in the NH. Based on the constructed stack, we identified and categorized 15 notable Holocene centennial cooling events (HCCEs) in the NH (period with temperature decreases). To test the chronological validity of the constructed HCCEs, we compared them with the most accurately dated and highly resolved climate records during the last 3 kyr, which have been extensively investigated by the scientific community. Based on the close alignment of the outlined HCCEs with temperature records, we suggest that other HCCEs also match centennial climate cooling events over the last 10 kyr. To understand the origins of the established HCCEs, we compared them with potential climate influencing factors: total solar irradiance (TSI), explosive volcanic activity, Atlantic meridional overturning circulation (AMOC)-limited slowdowns, Intertropical Convergence Zone (ITCZ) fluctuations, and El Niño/Southern Oscillation (ENSO variability. Early Holocene HCCE 5, terminated by a prominent 8.2-ka cold event, was likely driven by the superposition of the AMOC limited slowdown, TSI minimum, and volcanic activity. The Holocene Thermal Maximum (HTM) happened between HCCEs 5 and 4a and was interrupted by HCCE 4c and 4b, coeval, with a significant southward shift of the ITCZ, likely related to cooling in the tropical zone. However, the sequence of HCCEs 3b, 3a, and 2b (over 4.53–3.42 BP), accompanied by small changes in the TSI, was likely forced by an increase in ENSO variability, leading to remarkable changes in the tropical processes and a southward shift of the ITCZ, coeval with the collapse of the Chinese Neolithic cultures and onset of the Holocene Neoglacial. Subsequent HCCEs 2a–0a were likely forced by the TSI minimum combined with the influence of ENSO and volcanism over the last 2 ka. [ABSTRACT FROM AUTHOR]

The Arctic region is experiencing more rapid climate changes than the other parts of the world and serves as a sink for semi‐volatile persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), which can be utilized as molecular markers for pyrogenic carbon, such as black carbon (BC). As the sea ice retreats and increased terrestrial inputs with widespread wildfires, the PAH concentrations in the Arctic Ocean are rising. In this study, the sources and fates of PAHs together with BC in surface sediments from the East Siberian Arctic Shelf (ESAS) were analyzed. Positive matrix factorization (PMF) elucidated a mixed petrogenic and pyrogenic sources and distinct PAH fates associated with diverse input pathways including coastal permafrost erosion contribution (∼30%), petrogenic‐related emission (∼34%), fossil fuel combustion (∼26%), and biomass burning (∼10%). Correlation analysis indicated that BC plays a key role in affecting the behavior and fates of PAHs. In the Chukchi Sea, PAHs are closely associated with soot‐BC, whereas in the Laptev Sea (LS) and west East Siberian Sea (W‐ESS), they exhibit a coupling process with char‐BC. The presence of these carbonaceous materials in the sediments of CS is likely influenced by atmospheric deposition and biological activity, whereas the LS and W‐ESS regions are mainly affected by long‐distance river transport and direct deposition from coastal permafrost. As global warming continues, permafrost thawing induces the remobilization and retranslocation of PAHs, thereby becoming a significant PAH contributor and input pathway in the rapidly changing Arctic coastal margin. Plain Language Summary: The Arctic region is experiencing rapid climate changes, such as reducing sea ice, thawing permafrost, and increasing wildfires. These changes are raising the levels of semi‐volatile pollutants such as polycyclic aromatic hydrocarbons (PAHs) in the Arctic coastal margins, with the potential for the region to become a significant reservoir of sedimentary PAHs. In our study, we examined the large‐scale distribution and fates of PAHs and black carbon (BC) across the East Siberian Arctic Shelf (ESAS), the world's largest shelf system. We discovered that PAHs have mixed sources, including both petrogenic and pyrogenic origins. We also observed differences in how PAHs were transported and sequestrated in coastal versus open sea areas. In the western ESAS, PAHs and BC are mainly influenced by terrestrial inputs such as river discharge and coastal permafrost erosion. In contrast, in the eastern open‐sea regions, they are primarily constrained by atmospheric transport and biological activity are the primary influencing factors. The significant emissions from thawing permafrost along the coasts highlight the growing importance of permafrost‐related erosion as a significant contributor of PAHs in the Arctic Ocean, particularly in the context of future warming. Key Points: Sedimentary polycyclic aromatic hydrocarbons (PAHs) in the East Siberian Arctic Shelf (ESAS) have a mixture of petrogenic and pyrogenic sources with distinct input pathwaysPermafrost erosion serves as a significant input pathway and PAHs contributor in the rapidly changing Arctic coastsBlack carbon plays a key role in the behavior and sequestration of pyrogenic PAHs in the Arctic coastal margins [ABSTRACT FROM AUTHOR]

The secondary transporters of the resistance-nodulation-cell division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria like Pseudomonas aeruginosa. Among these RND transporters, MexB, MexF, and MexY, with partly overlapping specificities, have been implicated in pathogenicity. Only the structure of the former has been resolved experimentally, which together with the lack of data about the functional dynamics of the full set of transporters, limited a systematic investigation of the molecular determinants defining their peculiar and shared features. In a previous work (Ramaswamy et al., Front. Microbiol., 2018, 9, 1144), we compared at an atomistic level the two main putative recognition sites (named access and deep binding pockets) of MexB and MexY. In this work, we expand the comparison by performing extended molecular dynamics (MD) simulations of these transporters and the pathologically relevant transporter MexF. We employed a more realistic model of the inner phospholipid membrane of P. aeruginosa and more accurate force-fields. To elucidate structure/dynamics-activity relationships we performed physico-chemical analyses and mapped the binding propensities of several organic probes on all transporters. Our data revealed the presence, also in MexF, of a few multifunctional sites at locations equivalent to the access and deep binding pockets detected in MexB. Furthermore, we report for the first time about the multidrug binding abilities of two out of five gates of the channels deputed to peripheral (early) recognition of substrates. Overall, our findings help to define a common “recognition topology” characterizing Mex transporters, which can be exploited to optimize transport and inhibition propensities of antimicrobial compounds.

As a major reservoir of heat and CO2, the Pacific Ocean is an important component of the global climate system, but the nature of its circulation under different climatic conditions remains poorly understood. We present sedimentary records of surface water hydrography and nutrient dynamics from the subarctic Pacific Ocean, with the aim of investigating changes in sea-ice coverage, biological productivity, and sea surface temperature in the subarctic Northwest Pacific since 32 kyr. Our records indicate an enhanced North Pacific surface water stratification from the last glacial to Heinrich Stadial 1, which generally limited the siliceous productivity supply to the surface water. A productivity peak during the Bølling/Allerød warm interval was associated with an increase in the atmospheric pCO2, and it was driven by the increased supply of nutrient- and CO2-rich waters. This process can be attributed to the collapse of the North Pacific Intermediate Water formation at the onset of the Bølling/Allerød interstadial. Moreover, a northward shift of the westerly winds and the gyre boundary could have modulated the expansion of the subpolar gyre, driving changes in poleward heat transport, biogeochemistry, and the hydroclimate of the North Pacific. Our results are consistent with modern evidence for a northward shift of the westerlies in response to global warming, which will likely result in CO2 outgassing from the subarctic Pacific Ocean in the future.

Radiopharmaceuticals are currently a key tool in cancer diagnosis and therapy. Metal-based radiopharmaceuticals are characterized by a radiometal–chelator moiety linked to a bio-vector that binds the biological target (e.g., a protein overexpressed in a particular tumor). The right match between radiometal and chelator influences the stability of the complex and the drug's efficacy. Therefore, the coupling of the radioactive element to the correct chelator requires consideration of several features of the radiometal, such as its oxidation state, ionic radius, and coordination geometry. In this work, we systematically investigated about 120 radiometal–chelator complexes taken from the Cambridge Structural Database. We considered 25 radiometals and about 30 chelators, featuring both cyclic and acyclic geometries. We used quantum mechanics methods at the density functional theoretical level to generate the general AMBER force field parameters and to perform 1 µs-long all-atom molecular dynamics simulations in explicit water solution. From these calculations, we extracted several key molecular descriptors accounting for both electronic- and dynamical-based properties. The whole workflow was carefully validated, and selected test-cases were investigated in detail. Molecular descriptors and force field parameters for the complexes considered in this study are made freely available, thus enabling their use in predictive models, molecular modelling, and molecular dynamics investigations of the interaction of compounds with macromolecular targets. Our work provides new insights in understanding the properties of radiometal–chelator complexes, with a direct impact for rational drug design of this important class of drugs. [ABSTRACT FROM AUTHOR]

AbstractWildfire is an integral part of the Earth’s climate system and plays an important role in shaping terrestrial ecosystems and biodiversity, atmospheric chemistry, regional climate, and the carbon cycle in the Earth’s history. However, the lack of high-resolution records of long wildfires limits our understanding of the natural variability, long-term trends of wildfire activity, and the reasons behind the changes in wildfire on orbital timescales. Here, a 320 ka long high-resolution wildfire record from the subarctic North Pacific is reconstructed with black carbon (BC), including its two subtypes char and soot. A 7-day-long back trajectory simulation analysis reveals the higher frequency of trajectories comes from Siberia. Our data show that continuous incidence of wildfire on a continental scale over the last 320 ka was higher during glacial periods than during the interglacial periods. The increase in wildfire frequency during glacial periods is ascribed to less precipitation. Contrasting patterns of wildfire incidence between marine isotope stages 2 and 6 may be ascribed to different fuel availability, which is related to contrasting configurations of the Northern Hemisphere ice sheet between glacial periods. A significant periodicity of 23 ka of our wildfire record suggests the precession of the Earth’s orbit pace wildfire development. The tight coupling of intensified wildfire and enhanced nutrient utilization efficiency suggests a nontrivial role of fire in the climate system.

Abstract We investigated an alkenone-based sea surface temperature (SST) and the hydrographic change records of the subarctic Northwestern (NW) Pacific from the last glacial to interglacial. The core we investigated is a piston core (LV 63-41-2, 52.56° N, 160.00° E; water depth 1924 m) retrieved from the southern offshore east coast of the Kamchatka Peninsula, which is a location of high sedimentation rate, with highly dynamic interactions with the cold/warm water masses of the Bering Sea/the NW Pacific. Based on our alkenone analysis with a previously well-established chronology of the core, we found high glacial C37:4 contents suggesting larger freshwater influences prior to the last deglacial in approximately 27–16 ka BP. The most significant features of what we found are alkenone indicative of “warming” intervals with minimum alkenone productions that occurred prior to the stadial Heinrich event 1 and the Younger Dryas. In contrast, for the interval corresponding to the Bølling–Allerød period, our alkenone analysis shows relatively “colder” but maximum alkenone productions. We conclude that this particular subarctic alkenone SST proxy record is mainly masked by non-thermal environmental influences, such as strong shifts of timing and duration of the sea ice retreat and/or salinity changes in surface water at this site, which could cause changes in water stratification that affect nutrient supplies of the upper ocean that modulate growth durations of phytoplankton/coccolithophore productions. Our studies suggest that this subarctic alkenone “SST” proxy record is indicative of the changes of seasonality that control the timing and duration of the blooming seasons of coccolithophores. The alkenone “SST” proxy is also dominantly driven by water stratification effects that, instead of SSTs, reflect most likely a combination of the following local to regional climate and ocean current patterns: (1) the amount of meltwater inputs from high mountain glaciers at Kamchatka; (2) less saline, nutrient-rich Alaskan Stream waters from the Cordilleran Ice Sheet in the Gulf of Alaska; (3) downwelling waters associated with the interactions between the southward Eastern Kamchatka Current and the spinning-up of the North Pacific Subarctic Gyre; and (4) the strength of the Kuroshio Current since the last glacial.

With allowance made for the widespread prevalence of diffuse liver diseases, non-alcoholic fatty liver disease in particular, there is a need for the most objective evaluation of the state of this organ. One of the most important criteria for this evaluation is to estimate liver tissue density values. Today, the introduction of programs, such as lung cancer screening using low-dose computed tomography, has made it possible to conduct mass surveys in this area. This literature review deals with the advantages and disadvantages of computed tomography in detecting diffuse liver lesions.