bluuebunny/crossref_metadata_2025 huggingface dataset:
Saharan Dust Deposition in Central Europe in 2016—A Representative Year of the Increased North African Dust Removal Over the Last Decade
Authors: Rostási Ágnes , Topa Boglárka Anna , Gresina Fruzsina , Weiszburg Tamás G. , Gelencsér András , Varga György
Published: April 2022

Changes in circulation patterns associated with climate change have led to an increase in the frequency and intensity of Saharan dust events (SDEs) in the Carpathian Basin. The annual number of dust events was 4.2 on average between 1979 and 2010, while in the period of 2011–2018, it has increased to 10.3. This study presents a quantitative assessment of wet deposition of dust particles to Lake Balaton (Central Europe) with mineralogical and particle size distribution measurements. In addition to a comprehensive, systematic SDE identification process, rainwater samples were collected in 2016, and the particles on the filters were characterised using a range of analytical techniques. The atmospheric transport of particulates and moisture was evaluated using HYSPLIT Lagrangian trajectory model. XRD measurements revealed that during these events, the major minerals were quartz, kaolinite and 10-Å phyllosilicates. In addition, mineralogical source markers of arid dust (palygorskite and smectite) were also identified in majority of the analysed samples. Based on the results, wet deposition fluxes of dust particles were estimated for the region. 2016 was a typical and representative year for the decade, with twelve identified dust episodes. The synoptic patterns of the events fit well with the typical meteorological character of the North African dust intrusions with enhanced atmospheric meridionality described earlier. From the twelve episodes of 2016, seven were depositional events when wet deposition could be observed at ground level. Dust material of five episodes was analysed in detail, while particles of the two February wet deposition episodes were only granulometrically characterised. General uncertainties that hinder the characterisation of mineral dust in climate models were also observed in the granulometric and dust flux data of the sampled material. The particle size of the deposited dust was coarser than the upper cut-off level of grain size of the models. In addition, the discrepancies between measured and simulated deposition values clearly demonstrated the incorrect representation of dust flux in numerical simulations (partly due to inaccurate grain size data in the models).
Ambulatory Healthcare Use Profiles of Patients With Diabetes and Their Association With Quality of Care: A Cross-Sectional Study
Authors: Dupraz Julien , Zuercher Emilie , Taffé Patrick , Peytremann-Bridevaux Isabelle
Published: April 2022

Background

Despite the growing burden of diabetes worldwide, evidence regarding the optimal models of care to improve the quality of diabetes care remains equivocal. This study aimed to identify profiles of patients with distinct ambulatory care use patterns and to examine the association of these profiles with the quality of diabetes care.

Methods

We performed a cross-sectional study of the baseline data of 550 non-institutionalized adults included in a prospective, community-based, cohort study on diabetes care conducted in Switzerland. Clusters of participants with distinct patterns of ambulatory healthcare use were identified using discrete mixture models. To measure the quality of diabetes care, we used both processes of care indicators (eye and foot examination, microalbuminuria screening, blood cholesterol and glycated hemoglobin measurement [HbA1c], influenza immunization, blood pressure measurement, physical activity and diet advice) and outcome indicators (12-Item Short-Form Health Survey [SF-12], Audit of Diabetes-Dependent Quality of Life [ADDQoL], Patient Assessment of Chronic Illness Care [PACIC], Diabetes Self-Efficacy Scale, HbA1c value, and blood pressure <140/90 mmHg). For each profile of ambulatory healthcare use, we calculated adjusted probabilities of receiving processes of care and estimated adjusted outcomes of care using logistic and linear regression models, respectively.

Results

Four profiles of ambulatory healthcare use were identified: participants with more visits to the general practitioner [GP] than to the diabetologist and receiving concomitant podiatry care (“GP & podiatrist”, n=86); participants visiting almost exclusively their GP (“GP only”, n=195); participants with a substantially higher use of all ambulatory services (“High users”, n=96); and participants reporting more visits to the diabetologist and less visits to the GP than other profiles (“Diabetologist first”, n=173). Whereas participants belonging to the “GP only” profile were less likely to report most processes related to the quality of diabetes care, outcomes of care were relatively comparable across all ambulatory healthcare use profiles.

Conclusions

Slight differences in quality of diabetes care appear across the four ambulatory healthcare use profiles identified in this study. Overall, however, results suggest that room for improvement exists in all profiles, and further investigation is necessary to determine whether individual characteristics (like diabetes-related factors) and/or healthcare factors contribute to the differences observed between profiles.
Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes
Authors: Main Ailsa Maria , Benndorf Götz , Feldt-Rasmussen Ulla , Fugleholm Kåre , Kistorp Thomas , Loya Anand C. , Poulsgaard Lars , Rasmussen Åse Krogh , Rossing Maria , Sølling Christine , Klose Marianne Christina
Published: April 2022

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref <1.09 nmol/L) and a tumor biopsy confirmed the diagnosis of a paraganglioma. Phenoxybenzamine and Labetalol were used in high doses ((Dibenyline®, 90 mg x 3 daily) and labetalol (Trandate®, 200 + 300 + 300 mg daily) to stabilize blood pressure. The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.
Decoding the Therapeutic Implications of the ERα Stability and Subcellular Distribution in Breast Cancer
Authors: Tecalco-Cruz Angeles C. , Macías-Silva Marina , Ramírez-Jarquín Josué Orlando , Ramírez-Jarquín Uri Nimrod
Published: April 2022

Approximately 70% of all breast cancer cases are estrogen receptor-alpha positive (ERα+) and any ERα signaling pathways deregulation is critical for the progression of malignant mammary neoplasia. ERα acts as a transcription factor that promotes the expression of estrogen target genes associated with pro-tumor activity in breast cancer cells. Furthermore, ERα is also part of extranuclear signaling pathways related to endocrine resistance. The regulation of ERα subcellular distribution and protein stability is critical to regulate its functions and, consequently, influence the response to endocrine therapies and progression of this pathology. This minireview highlights studies that have deciphered the molecular mechanisms implicated in controlling ERα stability and nucleo-cytoplasmic transport. These mechanisms offer information about novel biomarkers, therapeutic targets, and promising strategies for breast cancer treatment.
Modeling Yield, Biogenic Emissions, and Carbon Sequestration in Southeastern Cropping Systems With Winter Carinata
Authors: Field John L. , Zhang Yao , Marx Ernie , Boote Kenneth J. , Easter Mark , George Sheeja , Hoghooghi Nahal , Johnston Glenn , Masum Farhad Hossain , Mulvaney Michael J. , Paustian Keith , Seepaul Ramdeo , Swan Amy , Williams Steve , Wright David , Dwivedi Puneet
Published: April 2022

Sustainable aviation fuel (SAF) production from lipids is a technologically mature approach for replacing conventional fossil fuel use in the aviation sector, and there is increasing demand for such feedstocks. The oilseed Brassica carinata (known as Ethiopian mustard or simply carinata) is a promising SAF feedstock that can be grown as a supplemental cash crop over the winter fallow season of various annual crop rotations in the Southeast US, avoiding land use changes and potentially achieving some of the soil carbon sequestration and ecosystem service benefits of winter cover crops. However, carinata may require more intensive management than traditional cover crops, potentially leading to additional soil greenhouse gas (GHG) emissions through increased carbon losses from soil tillage and nitrous oxide (N2O) emissions from nitrogen fertilizer application. In this work, the 2017 version of the process-based DayCent ecosystem model was used to establish initial expectations for the total regional SAF production potential and associated soil GHG emissions when carinata is integrated as a winter crop into the existing crop rotations across its current suitability range in southern Alabama, southern Georgia, and northern Florida. Using data from academic and industry carinata field trials in the region, DayCent was calibrated to reproduce carinata yield, nitrogen response, harvest index, and biomass carbon-to-nitrogen ratio. The resulting model was then used to simulate the integration of carinata every third winter across all 2.1 Mha of actively cultivated cropland in the study area. The model predicted regional average yields of 2.9–3.0 Mg carinata seed per hectare depending on crop management assumptions. That results in the production of more than two million Mg of carinata seed annually across the study area, enough to supply approximately one billion liters of SAF. Conventional management of carinata led to only modest increases in soil carbon storage that were largely offset by additional N2O emissions. Climate-smart management via adopting no-till carinata establishment or using poultry litter as a nitrogen source resulted in a substantial net soil GHG sink (0.23–0.31 Mg CO2e ha−1 y−1, or 0.24–0.32 Mg CO2e per Mg of seed produced) at the farms where carinata is cultivated.
Parks Under Stress: Air Temperature Regulation of Urban Green Spaces Under Conditions of Drought and Summer Heat
Authors: Kraemer Roland , Kabisch Nadja
Published: April 2022

In times of urbanization and climate change, urban green spaces and their ecosystem services are pivotal for adapting to extreme weather events such as heat and drought. But what happens to the provision of ecosystem services when green spaces themselves are compromised by heat and drought? In this study, we assessed the air temperature regulation by two structurally distinct inner-city parks in Leipzig, Germany, that were strongly affected by the heat and drought periods in 2018 and 2019. We used a dense network of in-situ measurements and machine learning to create spatially explicit maps of air temperature distribution at a fine-scale neighborhood level for a 24 h period during the summer heat wave in 2019. The results showed that the larger, tree-dominated park could maintain spaces of relative coolness at any time, whereas the other rather open, grass-dominated park was strongly heated during the daytime but provided relatively cool air during the night and early morning. We found a maximum spatially averaged cooling effect of green spaces versus the built-up surroundings of 1.1°C in the morning. In the afternoon, however, when air temperatures peaked at nearly 40°C, cooling was limited to shaded areas, leading to average differences between green spaces and built-up surroundings below 1°C. Our spatially explicit maps indicated that the “cooling distances” of green spaces, i.e., cooling effects that extend beyond the boundaries of a park, are negligible during dry and hot conditions. We conclude that vegetation structure, particularly the configuration of trees, is key to designing heat and drought-resilient green spaces and thus maintaining ecosystem service provision under the challenges of climate change. Urban planning needs to account for larger green spaces that are complemented by decentralized, well-distributed small-scale green infrastructure that intersperses the built infrastructure such as roadside greenery and vegetated backyards.
Effects of Stream Thermal Variability on Macroinvertebrate Community: Emphasis on Native Versus Non-Native Gammarid Species
Authors: Pander Joachim , Habersetzer Luis , Casas-Mulet Roser , Geist Juergen
Published: April 2022

An increase in river water temperatures is being detected worldwide, with some predictions of an up to 4°C rise by 2050. Such stream temperature increase is likely to affect aquatic communities, with predicted declines and range shifts of cold stenothermic species and a facilitated dispersal and population development in temperature-tolerant species, including invasive ones. This study analyzed how thermal changes affect macroinvertebrate community compositions in three differentiated thermal regions within a single stream system. In each thermal region, we used standard surber sampling in combination with in-stream cross-exposure experiments, comparing the thermal response of native vs. non-native gammarids (Gammarus roeselii and Dikerogammarus villosus). Macroinvertebrate species composition was highly dependent on temperature, with indigenous gammarids preferring colder sites and invasive ones such as D. villosus being dominant at higher temperatures. Species composition was also strongly affected by season, substratum and the presence of macrophytes. In light of climate change, consideration of shifts in community composition highly driven by temperature needs to become integrated with biological response patterns related to morphological and flow degradation, chemical pollution and fine sediment. Such an approach is crucial for the effective conservation and restoration of native biodiversity and for a realistic prediction of the ability to reach policy targets for aquatic ecosystems.
Systematic Evaluation of Physical Parameters Affecting the Terminal Settling Velocity of Microplastic Particles in Lakes Using CFD
Authors: Ahmadi Pouyan , Elagami Hassan , Dichgans Franz , Schmidt Christian , Gilfedder Benjamin S. , Frei Sven , Peiffer Stefan , Fleckenstein Jan H.
Published: April 2022

Microplastic (MP) particles are commonly found in freshwater environments such as rivers and lakes, negatively affecting aquatic organisms and potentially causing water quality issues. Understanding the transport and fate of MP particles in these environments is a key prerequisite to mitigate the problem. For standing water bodies (lakes, ponds) the terminal settling velocity (TSV) is a key parameter, which determines particle residence times and exposure times of organisms to MP in lakes. Here we systematically investigate the effects of the physical parameters density, volume, shape and roundness, surface roughness and hydrophobicity and lake water temperature on the TSV of a large number of particles with regular and irregular shapes (equivalent diameters: 0.5–2.5 mm) and different polymer densities using computational fluid dynamics (CFD) simulations. Simulation results are compared to laboratory settling experiments and used to evaluate existing, semi-empirical relationships to estimate TSV. The semi-empirical relationships were generally found to be in reasonable agreement with the CFD simulations (R2 > 0.92). Deviations were attributed to simplifications in their descriptions of particle shapes. Overall the CFD simulations also matched the TSVs from the experiments quite well, (R2 > 0.82), but experimental TSVs were generally slower than model TSVs with the largest differences for the irregular particles made from biodegradable polymers. The deviations of up to 58% were found to be related to the attachment of air bubbles on irregularities in the particle surfaces caused by the hydrophobicity of the MP particles. Overall, density was the most decisive parameter for TSV with increases in TSV of up to 400% followed by volume (200%), water temperature (47%) and particle roundness (45%). Our simulation results provide a frame of reference for an improved evaluation of the relative effects of different particle characteristics on their TSV in lakes. This will in turn allow a more robust estimation of particle residence times and potential exposure times of organism to MP in the different compartments of a lake.
The Evolution of Microbial Facilitation: Sociogenesis, Symbiogenesis, and Transition in Individuality
Authors: Zachar István , Boza Gergely
Published: April 2022

Metabolic cooperation is widespread, and it seems to be a ubiquitous and easily evolvable interaction in the microbial domain. Mutual metabolic cooperation, like syntrophy, is thought to have a crucial role in stabilizing interactions and communities, for example biofilms. Furthermore, cooperation is expected to feed back positively to the community under higher-level selection. In certain cases, cooperation can lead to a transition in individuality, when freely reproducing, unrelated entities (genes, microbes, etc.) irreversibly integrate to form a new evolutionary unit. The textbook example is endosymbiosis, prevalent among eukaryotes but virtually lacking among prokaryotes. Concerning the ubiquity of syntrophic microbial communities, it is intriguing why evolution has not lead to more transitions in individuality in the microbial domain. We set out to distinguish syntrophy-specific aspects of major transitions, to investigate why a transition in individuality within a syntrophic pair or community is so rare. We review the field of metabolic communities to identify potential evolutionary trajectories that may lead to a transition. Community properties, like joint metabolic capacity, functional profile, guild composition, assembly and interaction patterns are important concepts that may not only persist stably but according to thought-provoking theories, may provide the heritable information at a higher level of selection. We explore these ideas, relating to concepts of multilevel selection and of informational replication, to assess their relevance in the debate whether microbial communities may inherit community-level information or not.
Assessment of Environmental Flow Requirements for Four Major Chinese Carps in the Lower Reaches of the Jinsha River, Southwest China
Authors: Dai Lingquan , Wang Yu , Dai Huichao , Li Wei , Zheng Tiegang , Zhang Qingsen
Published: April 2022

An appropriate environmental flow (AEF) is one of the necessary conditions for fish spawning. The operation of cascade reservoirs in the lower reaches of the Jinsha River has changed the discharge process downstream, which in turn has directly affected the spawning habitat of fishes. Determining how to quantitatively evaluate the impact of different outflows from Xiangjiaba Reservoir on the spawning habitat of four major Chinese carp species in the downstream area is a key problem that must be solved immediately. The Yibin River section was selected as the study area, and the velocity and water depth were measured. A physical habitat simulation model (PHABSIM) was used to analyze the main hydrodynamic conditions that affect the spawning of the four major Chinese carp species and to quantify the weighted usable area (WUA) for the fishes based on different outflows from Xiangjiaba Reservoir. Hydrodynamic suitability curves for the four major Chinese carp species were established based on observed data from 2012 to 2020, and a two-dimensional hydrodynamic model was developed using a triangular grid to obtain the hydrodynamic distribution characteristics of the fish habitat. Then, the AEF range was obtained based on the outflow-WUA relationship. The results showed that the velocity during the spawning period was 0.6–1.3 m/s, the most appropriate velocity was 0.9–1.0 m/s, the water depth range was 3.0–18.0 m, and the most appropriate water depth was 9.0–12.0 m. Additionally, the AEF range was 2,000–4,500 m3/s, and the optimal AEF was, m3/s. The research results provide a scientific basis for the ecological operation of cascade reservoirs in the lower reaches of the Jinsha River.
Late Pleistocene–Holocene Palaeoenvironmental Evolution of the Makgadikgadi Basin, Central Kalahari, Botswana: New Evidence From Shallow Sediments and Ostracod Fauna
Authors: Franchi Fulvio , Cavalazzi Barbara , Evans Mary , Filippidou Sevasti , Mackay Ruaraidh , Malaspina Paolo , Mosekiemang Goitse , Price Alex , Rossi Veronica
Published: April 2022

The Makgadikgadi Basin in Botswana hosts a system of salt lakes, which developed from the Upper Pleistocene onward due to the gradual shrinking of the giant Lake Palaeo-Makgadikgadi. Stratigraphic and palaeoclimatic studies of this area are difficult due to the influence of several factors, such as a complex history of regional tectonic activities, as well as climatic changes coupled with dryland diagenetic processes. This lake, in the central Kalahari, is the key to understanding the climatic variability in the southern part of Africa in the Quaternary and has played an important role in the evolution of numerous taxa, including our own. In this study, detailed sedimentological analyses (grain size and major elements distribution) of shallow sediments from the Makgadikgadi Pans were combined with the first comprehensive study of the encountered ostracod fauna to establish trends in the environmental changes in the area from the late Quaternary. Ostracod fossil assemblages from the cores of the Makgadikgadi Pans are dominated by theLimnocytheressp., an opportunistic taxa commonly colonizing the littoral areas of shallow evaporative, ephemeral lakes, together with the subordinate occurrences ofSarcypridopsis ochracea,Sclerocypriscf.bicornis, Candonopsisspp., andIlyocyprisspp. The sediments from the pans show fluctuations in the Cl/K and Ca/Cl ratios, often in phase with the relative abundance ofLimnocytheresuggesting a cyclicity induced by changes of salinity and alkalinity in the water. This multi-proxy study of the cores collected from the pans suggests a Late Pleistocene shallow, playa lake environment with strongly alkaline water, interrupted by a prolonged drought with sustained aeolian conditions between ∼16 and 2 ka BP. Increasing diversity of ostracod fauna in the top 20–30 cm of the cores indicates that a temporary shift toward higher humidity occurred around 2–1.5 ka BP and lasted through the Medieval Warm Period. This humid period was followed by an overall desiccation trend that started with the Little Ice Age and continues until the present day.
Fluctuating Starvation Conditions Modify Host-Symbiont Relationship Between a Leaf Beetle and Its Newly Identified Gregarine Species
Authors: Wolz Marina , Rueckert Sonja , Müller Caroline
Published: April 2022

Gregarines are ubiquitous endosymbionts in invertebrates, including terrestrial insects. However, the biodiversity of gregarines is probably vastly underestimated and the knowledge about their role in shaping fitness-related traits of their host in dependence of fluctuating environmental conditions is limited. Using morphological and molecular analyses, we identified a new gregarine species, Gregarina cochlearium sp. n., in the mustard leaf beetle, Phaedon cochleariae. Applying a full-factorial design, we investigated the effects of a gregarine infection in combination with fluctuating starvation conditions during the larval stage on the development time and fitness-related traits of adult beetles. Under benign environmental conditions, the relationship between gregarines and the host seemed neutral, as host development, body mass, reproduction and survival were not altered by a gregarine infection. However, when additionally exposed to starvation, the combination of gregarine infection and this stress resulted in the lowest reproduction and survival of the host, which points to a parasitic relationship. Furthermore, when the host experienced starvation, the development time was prolonged and the adult females were lighter compared to non-starved individuals, independent of the presence of gregarines. Counting of gregarines in the guts of larvae revealed a lower gregarine load with increasing host body mass under stable food conditions, which indicates a regulation of the gregarine burden in dependence of the host condition. Contrary, in starved individuals the number of gregarines was the highest, hence the already weakened host suffered additionally from a higher gregarine burden. This interactive effect between gregarine infection and fluctuating starvation conditions led to an overall reduced fitness of P. cochleariae. Our study emphasizes the need to study endosymbionts as important components of the natural environment and to investigate the role of host-symbiont relationships under fluctuating environmental conditions in an evolutionary and ecological context.
Impact of Conservation Policies on Households’ Deforestation Decisions in Protected and Open-Access Forests: Cases of Moribane Forest Reserve and Serra Chôa, Mozambique
Authors: Massinga Jadwiga , Lisboa Sá Nogueira , Virtanen Pekka , Sitoe Almeida
Published: April 2022

Tropical deforestation is considered a global priority due to its environmental, social, and economic impacts at international, national, and household levels. Conservation policies constitute one of the pathways to reverse this scenario. This paper examines the influence of forest protection measures on local communities’ livelihood decisions regarding forest clearing. It compares deforestation, access to forest resources, and households’ strategies in protected and open-access forests: the Moribane Forest Reserve (MFR) and Serra Chôa (SCH), two environmentally sensitive areas with different conservation statuses in Manica Province, central Mozambique. Socioeconomic data were collected from September 2019 to August 2020 in 149 households in MFR and 144 households in SCH. The data were cross-examined with spatial information on deforestation from 2000 to 2020. We found that conservation status impacted household strategies, leading to less income source diversification and limited commercialization of forest products. In both areas, most respondents declared unlimited access to forest resources (89.9% for MFR and 68.8% for SCH), and the remaining proportion of respondents pointed out conservation, private forest, distance, and wildlife conflict as reasons for limited access. Shifting agriculture is the unique income source for 75.2% of the families in MFR and 28.4% in SCH. Most households in SCH diversify their income by combining shifting agriculture and livestock (68.75% against 24.8% in MFR). About 97% of the sampled households in MFR cleared forest for agriculture during the period 2000–2020, while 55.6% of the households cleared the forest in SCH during the same period. In MFR, non-timber forest products are mainly for subsistence use, except honey, which is sold by 52.2% of families. In SCH, commercialization of non-timber forest products is more diverse, with 11.1% of families selling honey, bush meat (5.5%), charcoal (3.4%), medicinal plants (2%), wood (1.3%), poles (11.1%), and firewood (12.5%). We conclude that the current conservation policies have little impact on household decisions to protect the forest, but they influence income diversification, leading to more dependency on agriculture and livestock.
Understanding the Genetic Diversity of Mycobacterium africanum Using Phylogenetics and Population Genomics Approaches
Authors: Balamurugan Muthukumar , Banerjee Ruma , Kasibhatla Sunitha Manjari , Achalere Archana , Joshi Rajendra
Published: April 2022

A total of two lineages of Mycobacterium tuberculosis var. africanum (Maf), L5 and L6, which are members of the Mycobacterium tuberculosis complex (MTBC), are responsible for causing tuberculosis in West Africa. Regions of difference (RDs) are usually used for delineation of MTBC. With increased data availability, single nucleotide polymorphisms (SNPs) promise to provide better resolution. Publicly available 380 Maf samples were analyzed for identification of “core-cluster-specific-SNPs,” while additional 270 samples were used for validation. RD-based methods were used for lineage-assignment, wherein 31 samples remained unidentified. The genetic diversity of Maf was estimated based on genome-wide SNPs using phylogeny and population genomics approaches. Lineage-based clustering (L5 and L6) was observed in the whole genome phylogeny with distinct sub-clusters. Population stratification using both model-based and de novo approaches supported the same observations. L6 was further delineated into three sub-lineages (L6.1–L6.3), whereas L5 was grouped as L5.1 and L5.2 based on the occurrence of RD711. L5.1 and L5.2 were further divided into two (L5.1.1 and L5.1.2) and four (L5.2.1–L5.2.4) sub-clusters, respectively. Unassigned samples could be assigned to definite lineages/sub-lineages based on clustering observed in phylogeny along with high-confidence posterior membership scores obtained during population stratification. Based on the (sub)-clusters delineated, “core-cluster-specific-SNPs” were derived. Synonymous SNPs (137 in L5 and 128 in L6) were identified as biomarkers and used for validation. Few of the cluster-specific missense variants in L5 and L6 belong to the central carbohydrate metabolism pathway which include His6Tyr (Rv0946c), Glu255Ala (Rv1131), Ala309Gly (Rv2454c), Val425Ala and Ser112Ala (Rv1127c), Gly198Ala (Rv3293) and Ile137Val (Rv0363c), Thr421Ala (Rv0896), Arg442His (Rv1248c), Thr218Ile (Rv1122), and Ser381Leu (Rv1449c), hinting at the differential growth attenuation. Genes harboring multiple (sub)-lineage-specific “core-cluster” SNPs such as Lys117Asn, Val447Met, and Ala455Val (Rv0066c; icd2) present across L6, L6.1, and L5, respectively, hinting at the association of these SNPs with selective advantage or host-adaptation. Cluster-specific SNPs serve as additional markers along with RD-regions for Maf delineation. The identified SNPs have the potential to provide insights into the genotype–phenotype correlation and clues for endemicity of Maf in the African population.
Aberrantly Expressed Small Noncoding RNAome in Keloid Skin Tissue
Authors: Yin Chuang , Wang Chuandong , Wang Chen
Published: April 2022

The skin is an organ that protects against injury and infection but can be damaged easily. Wound healing is a subtle balance which, if broken, can lead to keloid formation. Small noncoding (nc) RNAs can be of “housekeeping,” for example, ribosomal RNAs and transfer RNAs, or “regulatory,” for example, microRNAs (miRNAs or miRs), small nucleolar RNAs (snoRNAs), and P-element–induced Wimpy testis (PIWI)-interacting RNA (piRNA) types. We examined five types of small ncRNAs [miR, piRNA, snoRNA, small nuclear (sn) RNA, and repeat-associated small interfering RNA (rasiRNA)] in keloid skin tissue (KST) using sequencing and real-time reverse transcription-quantitative polymerase chain reaction. All comparisons were made in relation to expression in normal skin tissue (obtained by abdominoplasty). The expression of three piRNAs was upregulated, and the expression of six piRNAs was downregulated in KST. The expression of 12 snoRNAs was upregulated, and the expression of two snoRNAs was downregulated in KST. The expression of two snRNAs was downregulated in KST. The expression of 18 miRs was upregulated, and the expression of three miRNAs was downregulated in KST. The expression of one rasiRNA was upregulated, and the expression of one rasiRNA was downregulated in KST. We revealed the differential expression of small ncRNAs in KST, which may aid the development of new treatment for keloids.
Identification and Validation of Ferroptosis-Related Biomarkers in Septic Cardiomyopathy via Bioinformatics Analysis
Authors: Gong Cheng-Wu , Yuan Ming-Ming , Qiu Bai-Quan , Wang Li-Jun , Zou Hua-Xi , Hu Tie , Lai Song-Qing , Liu Ji-Chun
Published: April 2022

Septic cardiomyopathy (SCM) is a cardiac dysfunction caused by severe sepsis and septic shock that increases the risk of heart failure and death and its molecular mechanism remains unclear. Ferroptosis, a novel form of programmed cell death, has been reported to be present in the heart tissue of patients with sepsis, which demonstrated that ferroptosis may be a potential mechanism of myocardial injury in SCM. Therefore, we explored the role of ferroptosis-related genes (FRGs) in SCM and aimed to identify pivotal ferroptosis-related targets in SCM and potential therapeutic targets involved in the pathological process of SCM. To explore the regulatory mechanisms of ferroptosis in SCM, we identified differentially expressed genes (DEGs) in SCM and FRGs by bioinformatics analysis, and further identified hub genes. And the crucial microRNAs (miRNAs)-FRGs regulatory network was subsequently constructed. Finally, several candidate drugs associated with the hub genes were predicted, and Real-time quantitative reverse Transcription PCR (qRT-PCR) and western blotting analysis were performed to confirm the abnormal expression of hub genes. In this study, we identified several FRGs that may be involved in the pathogenesis of SCM, which helps us further clarify the role of ferroptosis in SCM and deeply understand the molecular mechanisms and potential therapeutic targets of SCM.
Spectrum of Genetic Variants in a Cohort of 37 Laterality Defect Cases
Authors: Antony Dinu , Gulec Yilmaz Elif , Gezdirici Alper , Slagter Lennart , Bakey Zeineb , Bornaun Helen , Tanidir Ibrahim Cansaran , Van Dinh Tran , Brunner Han G. , Walentek Peter , Arnold Sebastian J. , Backofen Rolf , Schmidts Miriam
Published: April 2022

Laterality defects are defined by the perturbed left–right arrangement of organs in the body, occurring in a syndromal or isolated fashion. In humans, primary ciliary dyskinesia (PCD) is a frequent underlying condition of defective left–right patterning, where ciliary motility defects also result in reduced airway clearance, frequent respiratory infections, and infertility. Non-motile cilia dysfunction and dysfunction of non-ciliary genes can also result in disturbances of the left–right body axis. Despite long-lasting genetic research, identification of gene mutations responsible for left–right patterning has remained surprisingly low. Here, we used whole-exome sequencing with Copy Number Variation (CNV) analysis to delineate the underlying molecular cause in 35 mainly consanguineous families with laterality defects. We identified causative gene variants in 14 families with a majority of mutations detected in genes previously associated with PCD, including two small homozygous CNVs. None of the patients were previously clinically diagnosed with PCD, underlining the importance of genetic diagnostics for PCD diagnosis and adequate clinical management. Identified variants in non-PCD-associated genes included variants in PKD1L1 and PIFO, suggesting that dysfunction of these genes results in laterality defects in humans. Furthermore, we detected candidate variants in GJA1 and ACVR2B possibly associated with situs inversus. The low mutation detection rate of this study, in line with other previously published studies, points toward the possibility of non-coding genetic variants, putative genetic mosaicism, epigenetic, or environmental effects promoting laterality defects.
Development of a TaqMan® Allelic Discrimination qPCR Assay for Rapid Detection of Equine CXCL16 Allelic Variants Associated With the Establishment of Long-Term Equine Arteritis Virus Carrier State in Stallions
Authors: Thieulent Come J. , Carossino Mariano , Balasuriya Udeni B. R. , Graves Kathryn , Bailey Ernest , Eberth John , Canisso Igor F. , Andrews Frank M. , Keowen Michael L. , Go Yun Young
Published: April 2022

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. Following natural infection, up to 70% of the infected stallions can remain persistently infected over 1 year (long-term persistent infection [LTPI]) and shed EAV in their semen. Thus, the LTP-infected stallions play a pivotal role in maintaining and perpetuating EAV in the equine population. Previous studies identified equine C-X-C motif chemokine ligand 16 (CXCL16) as a critical host cell factor determining LTPI in the stallion’s reproductive tract. Two alleles (CXCL16S and CXCL16r) were identified in the equine population and correlated with the susceptibility or resistance of a CD3+ T cell subpopulation in peripheral blood to in vitro EAV infection, respectively. Interestingly, CXCL16S has been linked to the establishment of LTPI in stallions, and thus, genotyping stallions based on CXCL16S/r would allow identification of those at the highest risk of establishing LTPI. Thus, we developed a TaqMan® allelic discrimination qPCR assay for the genotyping of the equine CXCL16 gene based on the identification of a single nucleotide polymorphism in position 1,073 based on NCBI gene ID: 100061442 (or position 527 based on Ensembl: ENSECAG00000018406.2) located in exon 2. One hundred and sixty horses from four breeds were screened for the CD3+ T cell susceptibility phenotype to EAV infection by flow cytometry and subsequently sequenced to determine CXCL16 allelic composition. Genotyping by Sanger sequencing determined that all horses with the resistant CD3+ T cell phenotype were homozygous for CXCL16r while horses with the susceptible CD3+ T cell phenotype carried at least one CXCL16S allele or homozygous for CXCL16S. In addition, genotypification with the TaqMan® allelic discrimination qPCR assay showed perfect agreement with Sanger sequencing and flow cytometric analysis. In conclusion, the new TaqMan® allelic discrimination genotyping qPCR assay can be used to screen prepubertal colts for the presence of the CXCL16 genotype. It is highly recommended that colts that carry the susceptible genotype (CXCL16 S/S or CXCL16S/r) are vaccinated against EAV after 6 months of age to prevent the establishment of LTPI carriers following possible natural infection with EAV.
Whole Exome Sequencing Identifies Genes Associated With Non-Obstructive Azoospermia
Authors: Zhang Hongguo , Li Wei , Jiang Yuting , Li Jia , Chen Mucheng , Wang Ruixue , Zhao Jing , Peng Zhiyu , Huang Hui , Liu Ruizhi
Published: April 2022

Background: Non-obstructive azoospermia (NOA) affects nearly 1% of men; however, the landscape of the causative genes is largely unknown.

Objective: To explore the genetic etiology which is the fundamental cause of NOA, a prospective case-control study and parental–proband trio linkage analysis were performed.

Materials: A total of 133 patients with clinicopathological NOA and 343 fertile controls were recruited from a single large academic fertility center located in Northeast China; in addition, eleven trio families were available and enrolled.

Results: Whole exome sequencing-based rare variant association study between the cases and controls was performed using the gene burden association testing. Linkage analysis on the trio families was also interrogated. In total, 648 genes were identified to be associated with NOA (three of which were previously reported), out of which six novel genes were found further associated based on the linkage analysis in the trio families, and involved in the meiosis-related network.

Discussion and Conclusion: The six currently identified genes potentially account for a fraction (3.76%, 5 out of 133 patients) of the heritability of unidentified NOA, and combining the six novel genes and the three previously reported genes together would potentially account for an overall 6.77% (9 out of 133 patients) heritability of unidentified NOA in this study.
BNT162b2, mRNA-1273, and Sputnik V Vaccines Induce Comparable Immune Responses on a Par With Severe Course of COVID-19
Authors: Kaznadzey Anna , Tutukina Maria , Bessonova Tatiana , Kireeva Maria , Mazo Ilya
Published: April 2022

Vaccines against the severe acute respiratory syndrome coronavirus 2, which have been in urgent need and development since the beginning of 2020, are aimed to induce a prominent immune system response capable of recognizing and fighting future infection. Here we analyzed the levels of IgG antibodies against the receptor-binding domain (RBD) of the viral spike protein after the administration of three types of popular vaccines, BNT162b2, mRNA-1273, or Sputnik V, using the same ELISA assay to compare their effects. An efficient immune response was observed in the majority of cases. The obtained ranges of signal values were wide, presumably reflecting specific features of the immune system of individuals. At the same time, these ranges were comparable among the three studied vaccines. The anti-RBD IgG levels after vaccination were also similar to those in the patients with moderate/severe course of the COVID-19, and significantly higher than in the individuals with asymptomatic or light symptomatic courses of the disease. No significant correlation was observed between the levels of anti-RBD IgG and sex or age of the vaccinated individuals. The signals measured at different time points for several individuals after full Sputnik V vaccination did not have a significant tendency to lower within many weeks. The rate of neutralization of the interaction of the RBD with the ACE2 receptor after vaccination with Sputnik V was on average slightly higher than in patients with a moderate/severe course of COVID-19. The importance of the second dose administration of the two-dose Sputnik V vaccine was confirmed: while several individuals had not developed detectable levels of the anti-RBD IgG antibodies after the first dose of Sputnik V, after the second dose the antibody signal became positive for all tested individuals and raised on average 5.4 fold. Finally, we showed that people previously infected with SARS-CoV-2 developed high levels of antibodies, efficiently neutralizing interaction of RBD with ACE2 after the first dose of Sputnik V, with almost no change after the second dose.
The Give-and-Take Interaction Between the Tumor Microenvironment and Immune Cells Regulating Tumor Progression and Repression
Authors: Pernot Simon , Evrard Serge , Khatib Abdel-Majid
Published: April 2022

A fundamental concern of the majority of cancer scientists is related to the identification of mechanisms involved in the evolution of neoplastic cells at the cellular and molecular level and how these processes are able to control cancer cells appearance and death. In addition to the genome contribution, such mechanisms involve reciprocal interactions between tumor cells and stromal cells within the tumor microenvironment (TME). Indeed, tumor cells survival and growth rely on dynamic properties controlling pro and anti-tumorigenic processes. The anti-tumorigenic function of the TME is mainly regulated by immune cells such as dendritic cells, natural killer cells, cytotoxic T cells and macrophages and normal fibroblasts. The pro-tumorigenic function is also mediated by other immune cells such as myeloid-derived suppressor cells, M2-tumor-associated macrophages (TAMs) and regulatory T (Treg) cells, as well as carcinoma-associated fibroblasts (CAFs), adipocytes (CAA) and endothelial cells. Several of these cells can show both, pro- and antitumorigenic activity. Here we highlight the importance of the reciprocal interactions between tumor cells and stromal cells in the self-centered behavior of cancer cells and how these complex cellular interactions control tumor progression and repression.
Case Report: A Novel CXCR4 Mutation in a Chinese Child With Kawasaki Disease Causing WHIM Syndrome
Authors: Ma Xiaopeng , Wang Yaping , Wu Peng , Kang Meiyun , Hong Yue , Xue Yao , Chen Chuqin , Li Huimin , Fang Yongjun
Published: April 2022

WHIM syndrome, an extremely rare congenital disease with combined immunodeficiency, is mainly caused by heterozygous gain-of-function mutation in the CXCR4 gene. There have been no previous case reports of WHIM syndrome with Kawasaki disease. We herein report a case of a boy who developed Kawasaki disease at the age of 1 year. After treatment, the number of neutrophils in his peripheral blood decreased continuously. His medical history revealed that he had been suffering from leukopenia, neutropenia and low immunoglobulin since birth, and his neutrophils could return to the normal level in the presence of infection or inflammation. Clinical targeted gene sequencing of 91 genes associated with granulocyte-related disease revealed that the patient had a novel heterozygous NM_003467; c.1032_1033delTG;p.(E345Vfs*12) variant in exon 2 of CXCR4 gene. Family verification analysis by Sanger sequencing showed that his father also had heterozygous variation at this site, while other family members did not. The computer prediction software indicated that the variation had a high pathogenicity. The computational structure analysis of the mutant revealed significant structural and functional changes in the CXCR4 protein. It should be noted that when unexplained persistent neutropenia with low immunoglobulin occurs after birth, especially when there is a family history of neutropenia, immunodeficiency should be investigated with genetic testing.