bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple congenital malformations arise from somatic mosaicism for constitutively active Pik3ca signaling
Authors: Marechal Elise , Poliard Anne , Henry Kilian , Moreno Mathias , Legrix Mathilde , Macagno Nicolas , Mondielli Grégoire , Fauquier Teddy , Barlier Anne , Etchevers Heather C.
Published: October 2022

Recurrent missense mutations of the PIK3CA oncogene are among the most frequent drivers of human cancers. These often lead to constitutive activation of its product p110α, a phosphatidylinositol 3-kinase (PI3K) catalytic subunit. In addition to causing a broad range of cancers, the H1047R mutation is also found in affected tissues of a distinct set of congenital tumors and malformations. Collectively termed PIK3CA-related disorders (PRDs), these lead to overgrowth of brain, adipose, connective and musculoskeletal tissues and/or blood and lymphatic vessel components. Vascular malformations are frequently observed in PRD, due to cell-autonomous activation of PI3K signaling within endothelial cells. These, like most muscle, connective tissue and bone, are derived from the embryonic mesoderm. However, important organ systems affected in PRDs are neuroectodermal derivatives. To further examine their development, we drove the most common post-zygotic activating mutation of Pik3ca in neural crest and related embryonic lineages. Outcomes included macrocephaly, cleft secondary palate and more subtle skull anomalies. Surprisingly, Pik3ca-mutant subpopulations of neural crest origin were also associated with widespread cephalic vascular anomalies. Mesectodermal neural crest is a major source of non-endothelial connective tissue in the head, but not the body. To examine the response of vascular connective tissues of the body to constitutive Pik3ca activity during development, we expressed the mutation by way of an Egr2 (Krox20) Cre driver. Lineage tracing led us to observe new lineages that had normally once expressed Krox20 and that may be co-opted in pathogenesis, including vascular pericytes and perimysial fibroblasts. Finally, Schwann cell precursors having transcribed either Krox20 or Sox10 and induced to express constitutively active PI3K were associated with vascular and other tumors. These murine phenotypes may aid discovery of new candidate human PRDs affecting craniofacial and vascular smooth muscle development as well as the reciprocal paracrine signaling mechanisms leading to tissue overgrowth.
The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in Drosophila
Authors: Serras Florenci
Published: October 2022

One of the main topics in regeneration biology is the nature of the early signals that trigger the damage response. Recent advances in Drosophila point to the MAP3 kinase Ask1 as a molecular hub that integrates several signals at the onset of regeneration. It has been discovered that reactive oxygen species (ROS) produced in damaged imaginal discs and gut epithelia will activate the MAP3 kinase Ask1. Severely damaged and apoptotic cells produce an enormous amount of ROS, which ensures their elimination by activating Ask1 and in turn the pro-apoptotic function of JNK. However, this creates an oxidative stress environment with beneficial effects that is sensed by neighboring healthy cells. This environment, in addition to the Pi3K/Akt nutrient sensing pathway, can be integrated into Ask1 to launch regeneration. Ultimately the activity of Ask1 depends on these and other inputs and modulates its signaling to achieve moderate levels of p38 and low JNK signaling and thus promote survival and regeneration. This model based on the dual function of Ask1 for early response to damage is discussed here.
Long-term environmental exposure of darkness induces hyperandrogenism in PCOS via melatonin receptor 1A and aromatase reduction
Authors: Chu Weiwei , Li Shang , Geng Xueying , Wang Dongshuang , Zhai Junyu , Lu Gang , Chan Wai-Yee , Chen Zi-Jiang , Du Yanzhi
Published: October 2022

Polycystic ovary syndrome (PCOS) is a common and complex disorder impairing female fertility, yet its etiology remains elusive. It is reported that circadian rhythm disruption might play a crucial role in PCOS pathologic progression. Here, in this research, we investigated the effect of environmental long-term circadian rhythm dysfunction and clarified its pathogenic mechanism in the development of PCOS, which might provide the targeted clinical strategies to patients with PCOS. Female SD rats were used to construct a circadian rhythm misalignment model with constant darkness (12/12-h dark/dark cycle), and the control group was kept under normal circadian rhythm exposure (12/12-h light/dark cycle) for 8 weeks. We measured their reproductive, endocrinal, and metabolic profiles at different zeitgeber times (ZTs). Different rescue methods, including melatonin receptor agonist and normal circadian rhythm restoration, and in vitro experiments on the KGN cell line were performed. We found that long-term darkness caused PCOS-like reproductive abnormalities, including estrous cycle disorder, polycystic ovaries, LH elevation, hyperandrogenism, and glucose intolerance. In addition, the expression of melatonin receptor 1A (Mtnr1a) in ovarian granulosa cells significantly decreased in the darkness group. Normal light/dark cycle and melatonin receptor agonist application relieved hyperandrogenism of darkness-treated rats. In vitro experiments demonstrated that decreased MTNR1A inhibited androgen receptor (AR) and CYP19A1 expression, and AR acted as an essential downstream factor of MTNR1A in modulating aromatase abundance. Overall, our finding demonstrates the significant influence of circadian rhythms on PCOS occurrence, suggests that MTNR1A and AR play vital roles in pathological progression of hyperandrogenism, and broadens current treatment strategies for PCOS in clinical practice.
Human Erysipelothrix rhusiopathiae infection via bath water – case report and genome announcement
Authors: Zautner Andreas E. , Tersteegen Aljoscha , Schiffner Conrad-Jakob , Ðilas Milica , Marquardt Pauline , Riediger Matthias , Delker Anna Maria , Mäde Dietrich , Kaasch Achim J.
Published: October 2022

Erysipelothrix rhusiopathiae is a facultative anaerobic, environmentally stable, Gram-positive rod that causes swine and avian erysipelas as a zoonotic pathogen. In humans, the main manifestations described are circumscribed erysipeloid, generalized erysipeloid, and endocarditis. Here, we report a 46-year-old female patient who presented to the physician because of redness and marked functio laesa of the hand, in terms of a pain-related restricted range of motion, and was treated surgically. E. rhusopathiae was detected in tissue biopsy. The source of infection was considered to be a pond in which both swine and, later, her dog bathed. The genome of the isolate was completely sequenced and especially the presumptive virulence associated factors as well as the presumptive antimicrobial resistance genes, in particular a predicted homologue to the multiple sugar metabolism regulator (MsmR), several predicted two-component signal transduction systems, three predicted hemolysins, two predicted neuraminidases, three predicted hyaluronate lyases, the surface protective antigen SpaA, a subset of predicted enzymes that potentially confer resistance to reactive oxygen species (ROS), several predicted phospholipases that could play a role in the escape from phagolysosomes into host cell cytoplasm as well as a predicted vancomycin resistance locus (vex23-vncRS) and three predicted MATE efflux transporters were investigated in more detail.
Telomere length and the risk of cardiovascular diseases: A Mendelian randomization study
Authors: Deng Yingjian , Li Qiang , Zhou Faguang , Li Guiyang , Liu Jianghai , Lv Jialan , Li Linlin , Chang Dong
Published: October 2022

Background

The causal direction and magnitude of the associations between telomere length (TL) and cardiovascular diseases (CVDs) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between TL and CVDs using Mendelian randomization (MR).

Materials and methods

In this two-sample MR study, we identified 154 independent TL-associated genetic variants from a genome-wide association study (GWAS) consisting of 472,174 individuals (aged 40–69) in the UK Biobank. Summary level data of CVDs were obtained from different GWASs datasets. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), Mendelian Randomization robust adjusted profile score (MR-RAPS), maximum likelihood estimation, weighted mode, penalized weighted mode methods, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to investigate the associations between TL and CVDs.

Results

Our findings indicated that longer TL was significantly associated with decreased risk of coronary atherosclerosis [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.75–0.95; P = 4.36E-03], myocardial infarction (OR, 0.72; 95% CI, 0.63–0.83; P = 2.31E-06), ischemic heart disease (OR, 0.87; 95% CI, 0.78–0.97; P = 1.01E-02), stroke (OR, 0.87; 95% CI, 0.79–0.95; P = 1.60E-03), but an increased risk of hypertension (OR, 1.12; 95% CI, 1.02–1.23; P = 2.00E-02). However, there was no significant association between TL and heart failure (OR, 0.94; 95% CI, 0.87–1.01; P = 1.10E-01), atrial fibrillation (OR, 1.01; 95% CI, 0.93–1.11; P = 7.50E-01), or cardiac death (OR, 0.95; 95% CI, 0.82–1.10; P = 4.80E-01). Both raw and outlier corrected estimates from MR-PRESSO were consistent with those of IVW results. The sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, P > 0.05), while Cochran’s Q test and MR-Egger suggested different degrees of heterogeneity.

Conclusion

Our MR study suggested that longer telomeres were associated with decreased risk of several CVDs, including coronary atherosclerosis, myocardial infarction, ischemic heart disease, and stroke, as well as an increased risk of hypertension. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
Comparison of outcomes between novel oral anticoagulants and warfarin monotherapy in patients with left atrial appendage closure: A systematic review and meta-analysis
Authors: Sun Bing , Chen Rui Rui , Gao Chao , Tao Ling
Published: October 2022

Background

Pivotal trials of percutaneous left atrial appendage closure (LAAC) used dedicated post-procedure antithrombotic protocols. However, there is no consensus on the selection of new oral anticoagulants (NOAC) and warfarin monotherapy after LAAC. This study aims to compare NOAC with warfarin monotherapy for efficacy and safety in patients undergoing LAAC.

Methods

A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared NOAC with warfarin monotherapy after LAAC. The effective outcomes included any major adverse events (all-cause death, stroke, major bleeding) and their individual components. Safety outcomes included all-cause death, major bleeding, total bleeding, DRT, and PDL >5 mm.

Results

We included 10 non-randomized clinical trials with 10,337 patients, of whom 4,960 patients received NOAC, while 5,377 patients received warfarin. There were no statistically significant differences in any major adverse events (LogOR: −0.11, 95% CI: −0.27, 0.04, P = 0.16), stroke (LogOR: 0.00, 95% CI: −0.42, 0.42, P = 1.00), all-cause death (LogOR: −0.23, 95% CI: −0.48, 0.02, P = 0.07), major bleeding (LogOR: −0.22, 95% CI: −0.45, 0.01, P = 0.06). NOAC was associated with a significant reduction in total bleeding (LogOR: −1.01, 95% CI: −1.47, −0.55, P < 0.0001) compared to warfarin. No statistically significant differences were found in DRT (LogOR: −0.19, 95% CI: −0.15, 0.52, P = 0.27) and PDL >5 mm (LogOR: 0.19, 95% CI: −0.33, 0.72, P = 0.47). Meta-regression and subgroup analysis showed that total bleeding (LogOR: −1.56, 95% CI: −2.15, −0.97, P < 0.001) was significantly lower in the NOAC group in the subgroup of <75 y.

Conclusion

After LAAC, NOAC monotherapy was associated with a lower risk of bleeding compared to warfarin monotherapy for 45 days. There was no significant difference between NOAC and warfarin in terms of other results.

Systematic review registration

www.york.ac.uk/inst/crd, identifier: CRD42022361244.
Estimation of the gas hydrate saturation from multichannel seismic data on the western continental margin of the Chukchi Rise in the Arctic Ocean
Authors: Choi Yeonjin , Kang Seung-Goo , Jin Young Keun , Hong Jong Kuk , Shin Sung-Ryul , Kim Sookwan , Choi Youngil
Published: October 2022

A multichannel seismic survey was conducted to investigate the geophysical characteristics of gas hydrates along the western continental margin of the Chukchi Rise around an ARAON mound cluster, which was first recovered in 2016. In the seismic data, gas hydrate-related bottom simulating reflection was widely distributed along the western continental margin of the Chukchi Rise. High-precision seismic P-wave velocity was obtained to investigate the geophysical characteristics of the gas hydrate structures in the BSR areas. Iterative migration velocity analysis was used to construct a detailed P-wave velocity model from the acquired seismic data. The gas hydrate and free gas layers have abnormally high- and low-seismic P-wave velocities; the precise velocity model allows us to understand the detailed spatial distribution of gas hydrate and free gas structures. The effective medium theory model enables estimations of the gas hydrate saturation from constructed seismic P-wave velocity model. We propose the P-wave velocity and gas hydrate saturation models from acquired multichannel seismic data in the western continental margin of the Chukchi Rise for the first time.
Contribution of anthropogenic vibration sources to crack growth in natural rock arches
Authors: Finnegan Riley , Moore Jeffrey R. , Geimer Paul R.
Published: October 2022

Natural arches are culturally valued rock landforms common in sedimentary rocks of the Colorado Plateau and additionally occur broadly around the world. Recent notable collapses of some of these landforms have highlighted the need to better understand the mechanics of their failure. While environmentally driven weathering has been the focus of most previous studies of arch collapse, comparably little attention has been given to anthropogenic vibration sources and how these often slight- to moderate-magnitude shaking events might steadily weaken arches over time. We collected 12–15 months of continuous ambient vibration data from arches and nearby bedrock in both anthropogenically ‘noisy’ and ‘quiet’ locations and used these datasets to develop an annual model of arch peak ground velocity based on magnitude-cumulative frequency distributions. Working from these models, we added vibration events of varying magnitude or frequency of occurrence, informed by field data, imitating arch vibration in response to different anthropogenic activities such as helicopter flights or induced earthquakes. We then applied subcritical fracture mechanics principles to predict annual crack growth rates in an idealized arch under these different vibration conditions. Our results demonstrate that in a single year, cracks grow minimally longer (∼1%) in ‘noisy’ environments than in areas not experiencing anthropogenic vibration energy. Few (1+) 30-s moderate-magnitude events (∼15 mm/s) or many (>37,000) 30-s low-magnitude events (∼2 mm/s) cause markedly increased crack growth. Our approach provides a valuable new framework for assessing the range and frequency of occurrence of vibrations experienced by an arch, and for predicting arch damage. Our results, in turn, yield important new outputs applicable in support of conservation management of these and similar landforms world-wide under exposure to a range of human-induced vibration activity.
Late Cryogenian and late Paleozoic ice ages on the São Francisco craton, east Brazil
Authors: Uhlein Gabriel J. , Uhlein Alexandre
Published: October 2022

The miniature paleocontinent in the region of the São Francisco River valley, in eastern Brazil, holds the record of two different glacial epochs. The late Cryogenian Jequitaí Formation from the Bambuí Group is up to 100 m thick and covers areas mainly in the central São Francisco craton. Evidences for glacial sedimentation are beautifully preserved E-W grooves and striations, dropstones within fine-grained rocks, and a full set of diamictites enclosing a rich and complex depositional history. The Jequitaí Formation is in close link with the tectonic evolution of the São Francisco paleocontinent and the West Gondwana amalgamation. From west, the precocious Paranapanema and São Francisco blocks collision in late Cryogenian flexured the foreland lithosphere and created depozones that were infilled by glacial sediments. Toward east, the rifting and opening of the Adamastor Ocean allowed thick glacial and non-glacial deposits to form through subaqueous gravitational sedimentation. From west to east, proximal and distal glaciomarine, glaciocontinental, and non-glacial resedimentation are identified and linked to the evolving continental masses and climate during the Cryogenian and beginning of Ediacaran. The late Paleozoic Santa Fé Group is the youngest record of glaciation on the São Francisco craton. It is 60–80 m thick and yields consistent and confident glacial evidences such as N-S striations on top of Cambrian sandstones, ice-rafted debris, and rain-out diamictite, all preserved in small and patchy areas in the west-central São Francisco craton. Paleocurrents suggest a northern ice center and sedimentary facies indicate deposition in continental lakes and rivers. Although late Paleozoic, its age is poorly constrained and likely correlated with the uppermost Itararé Group (Taciba Formation) of Paraná Basin in south Brazil. Deglaciation and strong isostatic adjustments make up the termination of the Santa Fé Group sedimentary record and depict a glaciocontinental system evolved on an interior stable continental crust. The late Neoproterozoic Jequitaí Formation and the late Paleozoic Santa Fé Group are parts of the earth’s sedimentary history preserving a rich record of climate, tectonic, and surface processes in part controlled by the evolving continental masses on the São Francisco craton.
TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis
Authors: Li Xue-Ying , Liu Zheng , Li Li , Wang Hai-Jun , Wang Hui
Published: October 2022

Background and aims

Findings about the associations between transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 and nonalcoholic fatty liver disease have not been consistently replicated, particularly in steatosis and fibrosis. The present study aimed to investigate the associations between the rs58542926T allele and the spectrum of NAFLD and its related metabolic phenotypes.

Methods

Systematic literature research was performed to analyse the associations between rs58542926 and the spectrum of NAFLD and its related metabolic phenotypes. A random effects meta-analysis with a dominant genetic model was applied.

Results

Data from 123,800 individuals across 44 studies were included in the current meta-analysis.rs58542926 T allele was associated with an increased risk of NAFLD in both adults (OR=1.62; 95% CI: 1.40, 1.86) and children (OR=2.87; 95% CI: 1.85, 4.46). Children had a stronger association with NAFLD (P=0.01). rs58542926 T allele was also positively associated with steatosis progression (mean difference=0.22; 95% CI: 0.05, 0.39) and fibrosis stage (OR=1.50; 95% CI: 1.20, 1.88) in adults. The TM6SF2 rs58542926 T allele was positively associated with ALT in both adults and children (both P<0.01) and only with higher AST in adults (P<0.01). The rs58542926 T allele was negatively associated with serum total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TGs) in both adults and children (all P<0.01).The serum level of TG was much lower in adults than in children (P<0.01).

Conclusion

TM6SF2 rs58542926 is involved in the entire spectrum of NAFLD and its related metabolic phenotype, and differences in serum lipid levels were observed between adults and children.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288163.
Bone-kidney axis: A potential therapeutic target for diabetic nephropathy
Authors: Yang Ming , Luo Shilu , Yang Jinfei , Chen Wei , He Liyu , Liu Di , Zhao Li , Wang Xi
Published: October 2022

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). However, its pathogenesis remains unclear, and effective prevention and treatment strategies are lacking. Recently, organ-to-organ communication has become a new focus of studies on pathogenesis. Various organs or tissues (the liver, muscle and adipose tissue) secrete a series of proteins or peptides to regulate the homeostasis of distal organs in an endocrine manner. Bone, an important part of the body, can also secrete bone-derived proteins or peptides that act on distal organs. As an organ with high metabolism, the kidney is responsible for signal and material exchange with other organs at any time through circulation. In this review, we briefly discussed bone composition and changes in bone structure and function in DN and summarized the current status of bone-derived proteins and their role in the progression of DN. We speculated that the “bone-kidney axis” is a potential target for early diagnosis and treatment of DN.
Obesity and periodontitis: A systematic review and updated meta-analysis
Authors: Kim Chang Min , Lee Soobin , Hwang Wonjun , Son Eunjeong , Kim Tae Woo , Kim Kihun , Kim Yun Hak
Published: October 2022

Background

A previous 2014 meta-analysis reported a positive association between obesity and periodontitis. It was considered necessary to update the recently published papers and to analyse subgroups on important clinical variables that could affect the association between obesity and periodontitis. Therefore, we updated the latest studies and attempted to derive more refined results.

Methods

All observational studies were eligible for inclusion. The Newcastle–Ottawa scale was used to qualitatively evaluate the risk of bias. Subgroup analyses were conducted for patients aged 18–34, 35–54, and 55+ years and the countries (European countries, USA, Brazil, Japan, Korea, and other Asian countries).

Results

Thirty-seven full-text articles were included. Obesity conferred increased odds of periodontal disease with an odds ratio (1.35, 95% CI: 1.05–1.75). In the subgroup analysis by age, the odds ratio was the highest in the 18–34 years group (2.21, 95% CI: 1.26–3.89). In the subgroup analysis by country, European countries had the highest odds ratio (2.46, 95% CI: 1.11–5.46).

Conclusion

Despite the differences in degree, a positive association between obesity and periodontitis was found regardless of country or age. Therefore, medical professionals should try to prevent periodontitis by controlling patient weights, and more studies should be conducted to determine the association between obesity and oral health.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022301343.
Adaptive damper control for HVAC systems based on human occupancy and indoor parameters: A development study
Authors: Vasanthkumar C. H. , Roselyn J. Preetha , Uthra R. Annie , Devaraj D.
Published: October 2022

Occupancy-based strategies for the control of ventilation systems in buildings are effective for achieving energy savings and user comfort. Savings in energy consumption of more than 50% can be achieved by controlling heat, ventilation, and air conditioning (HVAC) systems with accurate sensory and occupancy information. In this study, the flow through the damper of the variable area valve (VAV) system and the speed of the blower’s variable frequency drive (VFD) are controlled in the HVAC system, on the basis of human occupancy and indoor parameters, namely, temperature and humidity, segment-wise in the building. In the proposed model, the flapper angle of the VAV is estimated using the indoor temperature, external temperature, and number of occupants. The occupancy data are fed to the controller proposed to regulate the flow through the ducts of the system, which is based on the flapper angle of the VAV, in order to maintain human comfort. The proposed scheme makes it possible to detect abnormalities in energy utilization and to trace maximum utilization in the building based on occupancy, with the control parameters of the HVAC adjusted for a comfortable indoor environment. Performance evaluation of the VAV system with its proposed control strategy, temperature, and flow distribution is simulated using Fluent software. A laboratory grade prototype incorporating the proposed control strategy is then developed, tested under three different conditions, and the results are reported. The experimental results show that an energy saving of 18% can be achieved.
Geographical detector-based wheat quality attribution under genotype, environment, and crop management frameworks
Authors: Zhang Xueyan , Ma Xin , Li Yingchun , Ju Hui
Published: October 2022

Elucidating the determining factors for wheat quality is an essential but complex task, influenced by wheat cultivars, environmental conditions, and management decisions. This study analyzed 285 winter wheat varieties, 13 wheat quality traits, and 9 influencing factors under a genotype, environment, and crop management framework by a geographical detector model in China’s main winter wheat-producing area. Our results revealed the attribution of wheat quality in the genotype × environment × crop management (G × E × M) interaction framework. The factors influencing wheat quality in China were ranked as follows: wheat cultivar > precipitation > Tmax > irrigation > soil type > Tmin > fertiliser > sunshine duration > landform. The wheat cultivar was the dominant factor affecting wheat quality, which explained 38.57%, 38.78%, and 28.13% of the variation in gluten index, stabilization time, and sedimentation index, respectively. In addition, the sensitivity of the wheat quality traits to the G × E × M interaction framework was detected. The wheat quality trait sensitivity ranked from the highest to the lowest followed the order gluten index > sedimentation index > hardness index > stabilisation time > seed moisture > crude protein > formation time > wet gluten > water absorption > landing value > flour output ratio > ash > capacity. Gluten and sedimentation were highly sensitive traits for wheat quality under the G × E × M interaction framework, with sensitivity index values of 66.94% and 58.11% in the G × E × M framework, respectively. Furthermore, we proposed an integrated improvement strategy for an end-use wheat quality trait based on the sensitivity of wheat quality traits in the G × E × M framework. The gluten index, crude protein, wet gluten, and hardness index should be prioritized according to wheat’s commercial value and sensitivity index. However, other quality traits with higher commercial importance, such as flour output ratio, capacity, and landing value, should be put behind the improvement list. Our result identified the critical factors for most wheat quality traits in the G × E × M framework. It extended the comprehensive strategy for wheat quality improvement.
Cross-sectional use of barcode of life data system and GenBank as DNA barcoding databases for the advancement of museomics
Authors: Nakazato Takeru , Jinbo Utsugi
Published: October 2022

Museomics is an approach to the DNA sequencing of museum specimens that can generate both biodiversity and sequence information. In this study, we surveyed both the biodiversity information-based database BOLD (Barcode of Life System) and the sequence information database GenBank, by using DNA barcoding data as an example, with the aim of integrating the data from these two databases. DNA barcoding is a method of identifying species from DNA sequences by using short genetic markers. We surveyed how many entries had biodiversity information (such as links to BOLD and specimen IDs) by downloading all fish, insect, and flowering plant data available from the GenBank Nucleotide, and BOLD ID was assigned to 26.2% of entries for insects. In the same way, we downloaded the respective BOLD data and checked the status of links to sequence information. We also investigated how many species do these databases cover, and 7,693 species were found to exist only in BOLD. In the future, as museomics develops as a field, the targeted sequences will be extended not only to DNA barcodes, but also to mitochondrial genomes, other genes, and genome sequences. Consequently, the value of the sequence data will increase. In addition, various species will be sequenced and, thus, biodiversity information such as the evidence specimen photographs used as a basis for species identification, will become even more indispensable. This study contributes to the acceleration of museomics-associated research by using databases in a cross-sectional manner.
How do ectotherms perform in cold environments? Physiological and life-history traits in an Andean viviparous lizard
Authors: Clavijo-Baquet Sabrina , Orellana María J. , Sabat Pablo , Bozinovic Francisco
Published: October 2022

Both the mean and the variation in environmental temperature are increasing globally. Indeed, the predicted increases in temperature range from 2 to 4°C in the next 50 years. Ectotherms control body temperature by means of behavior selecting microsites with different temperatures, which makes them more susceptible to changes in climate. Nevertheless, lizards living in high mountain environments have developed several mechanisms to inhabit and colonize variable environments with extreme temperatures. These mechanisms include a high metabolism to be active at lower temperatures and viviparity to improve embryonic development. Despite behavioral thermoregulation acting as a buffer to changes in environmental temperature, other traits such as life-history traits may be less flexible. Consequently, in an attempt to understand how lizards cope with harsh habitats, we evaluated some physiological traits and responses of females of Liolaemus bellii from two contrasting slope sites with differences in environmental temperature and humidity, but at the same altitude in the southern Andes range. We collected pregnant females from opposite slopes and maintained them until parturition in a common-garden experiment. Females from the south-facing slope (S-slope) had higher preferred body temperature (Tpref) values before and after parturition and exhibited higher daily energy expenditure before parturition. Nevertheless, no difference in Tpref was shown by their offspring, suggesting a developmental plastic response or adaptation to lower environmental temperature. For instance, the higher metabolism during pregnancy could be associated with a shorter activity period on the snowy S-slope. Additionally, females from the S-slope had larger kidneys and gave birth later than N-slope females, likely due to developmental plasticity or genetic differentiation. How fixed these traits are, in individuals from the contrasting slopes, will determine the response capacity of the L. bellii population to climate change.
Chitosan and nematophagous fungi for sustainable management of nematode pests
Authors: Lopez-Nuñez Raquel , Suarez-Fernandez Marta , Lopez-Moya Federico , Lopez-Llorca Luis Vicente
Published: October 2022

Plants are exposed to large number of threats caused by herbivores and pathogens which cause important losses on crops. Plant pathogens such as nematodes can cause severe damage and losses in food security crops worldwide. Chemical pesticides were extendedly used for nematode management. However, due to their adverse effects on human health and the environment, they are now facing strong limitations by regulatory organisations such as EFSA (European Food Safety Authority). Therefore, there is an urgent need for alternative and efficient control measures, such as biological control agents or bio-based plant protection compounds. In this scenario, chitosan, a non-toxic polymer obtained from seafood waste mainly, is becoming increasingly important. Chitosan is the N-deacetylated form of chitin. Chitosan is effective in the control of plant pests and diseases. It also induces plants defence mechanisms. Chitosan is also compatible with some biocontrol microorganisms mainly entomopathogenic and nematophagous fungi. Some of them are antagonists of nematode pests of plants and animals. The nematophagous biocontrol fungus Pochonia chlamydosporia has been widely studied for sustainable management of nematodes affecting economically important crops and for its capability to grow with chitosan as only nutrient source. This fungus infects nematode eggs using hyphal tips and appressoria. Pochonia chlamydosporia also colonizes plant roots endophytically, stimulating plant defences by induction of salicylic and jasmonic acid biosynthesis and favours plant growth and development. Therefore, the combined use of chitosan and nematophagous fungi could be a novel strategy for the biological control of nematodes and other root pathogens of food security crops.
Microsatellite markers of the major histocompatibility complex genomic region of domestic camels
Authors: Knoll Ales , Wijacki Jan , Plasil Martin , Burger Pamela A. , Horin Petr
Published: October 2022

We identified and characterized 11 polymorphic microsatellite markers suitable for routine testing (three in the MHC class I sub-region, four in MHC class II and four in the MHC class III sub-region) of dromedaries and Bactrian camels. In total, 38 dromedaries and 33 Bactrian camels were genotyped, and interspecific differences were observed in the numbers of alleles and in allelic frequencies, as well as in the observed heterozygosity. These loci may be used as markers to study the adaptive genetic diversity of the MHC region in Old World camels.
Novel IKZF3 transcriptomic signature correlates with positive outcomes of skin cutaneous melanoma: A pan-cancer analysis
Authors: Yang Lin-Kai , Lin Can-Xiang , Li Sheng-Hong , Liang Jia-Ji , Xiao Li-Ling , Xie Guang-Hui , Liu Hong-Wei , Liao Xuan
Published: October 2022

To investigate the potential relationship between Ikaros family genes and skin cutaneous melanoma (SKCM), we undertook a pan-cancer analysis of the transcriptional signature and clinical data of melanoma through multiple databases. First, 10,327 transcriptomic samples from different cancers were included to determine the overall characteristics and clinical prognoses associated with Ikaros gene expression across cancer types. Second, differentially expressed genes analysis, prognostic evaluation, and gene set enrichment analysis were employed to investigate the role of Ikaros (IKZF) genes in SKCM. Third, we evaluated the relationship between Ikaros family genes and SKCM immune infiltrates and verified the findings using the GEO single-cell sequencing dataset. The results show that Ikaros genes were widely expressed among different cancer types with independently similar patterns as follows: 1. IKZF1 and IKZF3, and 2. IKZF2 and IKZF4–5. IKZF2 and IKZF5 were downregulated in the primary tumor, and IKZF1–3 expression decreased significantly as the T-stage or metastasis increased in SKCM. Moreover, high IKZF1–3 expression was associated with better overall survival, disease-specific survival, and progression-free interval. IKZF3 is an independent prognostic factor of SKCM. Among Ikaros genes, the expression of IKZF1 and IKZF3 positively correlated with the infiltration level of CD4+ T cells and CD8+ T cells, B cells, and Tregs in SKCM and negatively correlated with the infiltration level of M0 and M1 macrophages. Moreover, single-cell sequencing data analysis revealed that IKZF1 and IKZF3 were mainly expressed by immune cells. Correlation analysis shows the immune factors and drug responses associated with IKZF3 expression. In conclusion, the present study is the first, to our knowledge, to identify a pan-cancer genomic signature of the Ikaros gene family among different cancers. Expression of these family members, particularly high levels of IKZF3, indicate positive immunological status and beneficial clinical outcomes of SKCM. IKZF3 may therefore serve as potential targets for immunotherapy of melanoma.
High expression of MARVELD3 as a potential prognostic biomarker for oral squamous cell carcinoma
Authors: Huang Ke , Meng Yucheng , Lu Jiyuan , Xu Lingdan , Wang Shiqi , Wang Huihui , Xu Zhaoqing
Published: October 2022

Objectives: Tight junction-associated marvel proteins (TAMP) is a transmembrane protein whose members are associated with tight junctions between cells and epithelial remodeling. MARVEL domain containing 3 (MARVELD3) is one of the members of the TAMP. MARVELD3, as a novel tight junction protein involved in bicellular tight junction assembly, has attracted growing attention in the field of oncology. This study aimed to investigate the prognostic role of MARVELD3 and to determine how it functions in tumorigenesis in oral squamous cell carcinoma (OSCC), thus providing additional data to help the guidance of clinical practice.

Materials and Methods: RNA-seq data and relevant clinical information were obtained from TCGA. Bioinformatics means used in this study included differential gene expression analysis, KM survival curve analysis, univariate and multivariate Cox regression analyses, nomogram analysis, ROC curve analysis, methylation level analysis, gene function enrichment analysis, and immune cell infiltration analysis.

Results:MARVELD3 was significantly higher expressed in OSCC tissue than in normal tissue, and the overall survival of the high expression group was significantly lower than that of the normal group. Univariate and multivariate Cox regression analyses showed that MARVELD3 could serve as an independent contributing factor to poor OSCC prognosis. The nomograms and ROC curves supported the results above. Its expression was negatively correlated with DNA methylation sites. Analysis of PPI networking and gene functional enrichment showed that MARVELD3 was involved in the functional activities of DNA and RNA and was associated with immune cell infiltration.

Conclusion: The high expression of MARVELD3 is associated with poor prognosis in OSCC, and MARVELD3 could be recognized as a novel independent prognostic factor for OSCC.
Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
Authors: Li Miaomiao , Zhang Tianyang , Chen Wei
Published: October 2022

Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patients. The aberrant expression of necroptosis-related genes (NRGs) is reported to be associated with tumorigenesis and metastasis. In the present work, we compared the expression profiles of NRGs between COAD patients and normal individuals. Based on seven differentially expressed NRGs, a risk score was defined to predict the prognosis of COAD patients. The validation results from both training and independent external cohorts demonstrated that the risk score is able to distinguish the high and low risk COAD patients with higher accuracies, and is independent of the other clinical factors. To facilitate its clinical use, by integrating the proposed risk score, a nomogram was built to predict the risk of individual COAD patients. The C-index of the nomogram is 0.75, indicating the reliability of the nomogram in predicting survival rates. Furthermore, two candidate drugs, namely dapsone and xanthohumol, were screed out and validated by molecular docking, which hold the potential for the treatment of COAD. These results will provide novel clues for the diagnosis and treatment of COAD.
From the patient to the population: Use of genomics for population screening
Authors: Mighton Chloe , Shickh Salma , Aguda Vernie , Krishnapillai Suvetha , Adi-Wauran Ella , Bombard Yvonne
Published: October 2022

Genomic medicine is expanding from a focus on diagnosis at the patient level to prevention at the population level given the ongoing under-ascertainment of high-risk and actionable genetic conditions using current strategies, particularly hereditary breast and ovarian cancer (HBOC), Lynch Syndrome (LS) and familial hypercholesterolemia (FH). The availability of large-scale next-generation sequencing strategies and preventive options for these conditions makes it increasingly feasible to screen pre-symptomatic individuals through public health-based approaches, rather than restricting testing to high-risk groups. This raises anew, and with urgency, questions about the limits of screening as well as the moral authority and capacity to screen for genetic conditions at a population level. We aimed to answer some of these critical questions by using the WHO Wilson and Jungner criteria to guide a synthesis of current evidence on population genomic screening for HBOC, LS, and FH.
Advancing mRNA technologies for therapies and vaccines: An African context
Authors: Kairuz Dylan , Samudh Nazia , Ely Abdullah , Arbuthnot Patrick , Bloom Kristie
Published: October 2022

Synthetic mRNA technologies represent a versatile platform that can be used to develop advanced drug products. The remarkable speed with which vaccine development programs designed and manufactured safe and effective COVID-19 vaccines has rekindled interest in mRNA technology, particularly for future pandemic preparedness. Although recent R&D has focused largely on advancing mRNA vaccines and large-scale manufacturing capabilities, the technology has been used to develop various immunotherapies, gene editing strategies, and protein replacement therapies. Within the mRNA technologies toolbox lie several platforms, design principles, and components that can be adapted to modulate immunogenicity, stability, in situ expression, and delivery. For example, incorporating modified nucleotides into conventional mRNA transcripts can reduce innate immune responses and improve in situ translation. Alternatively, self-amplifying RNA may enhance vaccine-mediated immunity by increasing antigen expression. This review will highlight recent advances in the field of synthetic mRNA therapies and vaccines, and discuss the ongoing global efforts aimed at reducing vaccine inequity by establishing mRNA manufacturing capacity within Africa and other low- and middle-income countries.
A novel risk score based on immune-related genes for hepatocellular carcinoma as a reliable prognostic biomarker and correlated with immune infiltration
Authors: Long Meiying , Zhou Zihan , Wei Xueyan , Lin Qiuling , Qiu Moqin , Zhou Yunxiang , Chen Peiqin , Jiang Yanji , Wen Qiuping , Liu Yingchun , Li Runwei , Zhou Xianguo , Yu Hongping
Published: October 2022

Background

Immunological-related genes (IRGs) play a critical role in the immune microenvironment of tumors. Our study aimed to develop an IRG-based survival prediction model for hepatocellular carcinoma (HCC) patients and to investigate the impact of IRGs on the immune microenvironment.

Methods

Differentially expressed IRGs were obtained from The Genomic Data Commons Data Portal (TCGA) and the immunology database and analysis portal (ImmPort). The univariate Cox regression was used to identify the IRGs linked to overall survival (OS), and a Lasso-regularized Cox proportional hazard model was constructed. The International Cancer Genome Consortium (ICGC) database was used to verify the prediction model. ESTIMATE and CIBERSORT were used to estimate immune cell infiltration in the tumor immune microenvironment (TIME). RNA sequencing was performed on HCC tissue specimens to confirm mRNA expression.

Results

A total of 401 differentially expressed IRGs were identified, and 63 IRGs were found related to OS on the 237 up-regulated IRGs by univariate Cox regression analyses. Finally, five IRGs were selected by the LASSO Cox model, including SPP1, BIRC5, STC2, GLP1R, and RAET1E. This prognostic model demonstrated satisfactory predictive value in the ICGC dataset. The risk score was an independent predictive predictor for OS in HCC patients. Immune-related analysis showed that the immune infiltration level in the high-risk group was higher, suggesting that the 5-IRG signature may play an important role in mediating immune escape and immune resistance in the TIME of HCC. Finally, we confirmed the 5-IRG signature is highly expressed in 65 HCC patients with good predictive power.

Conclusion

We established and verified a new prognosis model for HCC patients based on survival-related IRGs, and the signature could provide new insights into the prognosis of HCC.
SARS-CoV-2 ORF8: One protein, seemingly one structure, and many functions
Authors: Vinjamuri Smita , Li Lenong , Bouvier Marlene
Published: October 2022

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 encodes nine accessory proteins that are involved in host-pathogen interaction. ORF8 is unique among these accessory proteins. SARS-CoV-2 ORF8 shares a surprisingly low amino acid sequence similarity with SARS-COV ORF8 (30%), and it is presumed to have originated from bat. Studies have shown that ORF8 exerts multiple different functions that interfere with host immune responses, including the downregulation of MHC class I molecules. These functions may represent strategies of host immune evasion. The x-ray crystal structure of ORF8 revealed an immunoglobulin-like domain with several distinguishing features. To date, there are numerous unanswered questions about SARS-CoV-2 ORF8 protein and its structure-function relationship that we discuss in this mini-review. A better understanding of how ORF8 interacts with components of the immune system is needed for elucidating COVID-19 pathogenesis and to develop new avenues for the treatment of the disease.
Unbalanced Arginine pathway and altered maturation of pleural macrophages in Th2-deficient mice during Litomosoides sigmodontis filarial infection
Authors: Remion Estelle , Gal Joséphine , Chaouch Soraya , Rodrigues Jules , Lhermitte-Vallarino Nathaly , Alonso Joy , Kohl Linda , Hübner Marc P. , Fercoq Frédéric , Martin Coralie
Published: October 2022

Filarial parasites are tissue dwelling worms transmitted by hematophagous vectors. Understanding the mechanisms regulating microfilariae (the parasite offspring) development is a prerequisite for controlling transmission in filarial infections. Th2 immune responses are key for building efficient anti-parasite responses but have been shown to also lead to detrimental tissue damage in the presence of microfilariae. Litomosoides sigmodontis, a rodent filaria residing in the pleural cavity was therefore used to characterize pleuropulmonary pathology and associated immune responses in wild-type and Th2 deficient mice. Wild-type and Th2-deficient mice (Il-4rα-/-/Il-5-/-) were infected with L. sigmodontis and parasite outcome was analyzed during the patent phase (when microfilariae are in the general circulation). Pleuropulmonary manifestations were investigated and pleural and bronchoalveolar cells were characterized by RNA analysis, imaging and/or flow cytometry focusing on macrophages. Il-4rα-/-/Il-5-/- mice were hypermicrofilaremic and showed an enhanced filarial survival but also displayed a drastic reduction of microfilaria-driven pleural cavity pathologies. In parallel, pleural macrophages from Il-4rα-/-/Il-5-/- mice lacked expression of prototypical alternative activation markers RELMα and Chil3 and showed an altered balance of some markers of the arginine metabolic pathway. In addition, monocytes-derived F4/80intermediate macrophages from infected Il-4rα-/-/Il-5-/- mice failed to mature into resident F4/80high large macrophages. Altogether these data emphasize that the presence of both microfilariae and IL-4R/IL-5 signaling are critical in the development of the pathology and in the phenotype of macrophages. In Il-4rα-/-/Il-5-/- mice, the balance is in favor of parasite development while limiting the pathology associated with the host immune response.