bluuebunny/crossref_metadata_2025 huggingface dataset:
KINERJA DINAS PEMBERDAYAAN MASYARAKAT DAN DESA DALAM MEWUJUDKAN PEMBERDAYAAN MASYARAKAT MELALUI PENGGUNAAN DANA DESA DI KABUPATEN BELU PROVINSI NUSA TENGGARA TIMUR
Authors: Taek Maximilianus Mario , Wasistiono Sadu , Meltarini Meltarini
Published: September 2021

The use of Village Funds is not appropriate and there are still problems so that it has not reduced the poverty rate, this is because the guidance is not maximized by the Belu Regency PMD Office. This study aims to analyze performance of the Community and Village Empowerment Service in realizing community empowerment through the use of Village Funds. The theory used is the performance of Sinambela Lijan (2012), with indicators of productivity, responsiveness, responsibility and accountability. The approach to data analysis is the SWOT analysis with the Litmus test. This study used qualitative research method with descriptive approach, data collection techniques: interviews (17 informants) and documentation. The findings of the study indicate that human resource capacity is still low, infrastructure is still limited, lack of cross-sectoral coordination, lack of community understanding and weak institutional capacity in the village. Conclusion: The performance of the Community and Village Empowerment Service is quite good, but there are still some problems so that the authors convey several strategic issues, namely increasing the capacity of employees as trainers and facilitators so that community empowerment is more effective and maximizes the potential in the village so that it can be used to support community empowerment activities, with the aim of realizing Village independence.

Keywords: Performance, Village Funds, Community Empowerment
IMPLEMENTASI KEBIJAKAN PEMBINAAN ANAK JALANAN, GELANDANGAN, PENGEMIS DAN PENGAMEN DI KOTA MAKASSAR PROVINSI SULAWESI SELATAN
Authors: Hidayah Endang Sri
Published: September 2021

Makassar City is a city that has various complex problems, including the existence of homeless youth, homelessness, beggars and Busker or street musicians. City development has become an attraction for the outside community so that it has an impact on the flow of urbanization, the population is increasing and it is difficult to find work in the city. This study aims to describe how the implementation of the Makassar City Regulation Number 2 of 2008 concerning Development of homeless youth, homelessness, beggars and Busker or street musicians, as well as to find out what strategies the Makassar City Government has implemented in dealing with homeless youth, homelessness, beggars and Busker or street musicians. The analysis conducted by researchers is using the theory of implementation of Van Meter and Van Horn with qualitative descriptive research methods with an inductive approach. To analyze the strategy, the researcher used a SWOT analysis to provide an alternative strategy. From the research results, it is concluded that the coaching has not been successful, there are still measures and policy objectives that have not been achieved, additional funding resources are needed for employees who go to the field every day, the characteristics of the implementing agencies in implementing this policy are adjusted to the objects found in the field. , although communication between organizations between Dinsos in collaboration with the Satpol PP, YKP2N and rehabilitation centers has been carried out quite well, the economic, social and political environment of the community has not played an active role in helping the City Government implement this policy. There are still many people with social illnesses who have been coached back to the streets, the attitude of the implementers has the principle of integrity coordination and synchronization both vertically and horizontally, although in practice it has not been carried out optimally. Based on the identification results of internal factors and external factors in the SWOT analysis, 9 (nine) strategic issues were generated.Keywords: implementation, policy, coaching, homelessness, city of Makassar.
The Leadership Role in The Smart-Village Program in Banyuwangi District, East Java
Authors: Wargadinata Ella Lesmanawaty'
Published: September 2021

The use of information communication technology (ICT) in government administration has changed the face of Weber's conventional bureaucracy into a modern model. The electronic or digital-based government model is an important milestone in this 21st century due to its ability to improve government performance, thereby increasing public satisfaction. The successful implementation of e-government is influenced by many beneficial and nonbeneficial determining factors, such as leadership. Therefore, this research aims to explore the leadership role of the Smart village program implemented in 2010 by the Banyuwangi District Government using a qualitative approach. Data were collected through observation in selected locations, interviews, and secondary sources. The data obtained were processed using the NVivo application process due to its ability to capture and build inductively concepts that describe research based on local perspectives. The results processed through the word cloud feature illustrate two interesting analyses. First Smart village is considered an online administration service by the Banyuwangi people because it is easy, fast, open, and full of certainty. Second leadership has 5 important roles, namely Charismatic, Innovative, Consistent, Cooperation, and Integrity. In conclusion, the success of e-government is strongly influenced by the usefulness of services for the community and the seriousness of the leadership to implement e-government not only as a political gimmick but to serve the community.

 

Keywords:  Digital service, Transformational Leadership, Digital Society, Openness
A Novel Biosorbent From Hardwood Cellulose Nanofibrils Grafted With Poly(m-Aminobenzene Sulfonate) for Adsorption of Cr(VI)
Authors: Yu Yong Ho , An Liangliang , Bae Jin Ho , Heo Ji Won , Chen Jiansong , Jeong Hanseob , Kim Yong Sik
Published: September 2021

Graphical Abstract

Biosorbent from cellulose nanofibrils grafted with poly(m-aminobenzene sulfonate) (PABS) was prepared for effective detoxification and adsorption of Cr(VI) in an aqueous medium.
Interkingdom Comparison of Threonine Metabolism for Stem Cell Maintenance in Plants and Animals
Authors: Sahoo Debee Prasad , Van Winkle Lon J. , Díaz de la Garza Rocío I. , Dubrovsky Joseph G.
Published: September 2021

In multicellular organisms, tissue generation, maintenance, and homeostasis depend on stem cells. Cellular metabolic status is an essential component of different differentiated states, from stem to fully differentiated cells. Threonine (Thr) metabolism has emerged as a critical factor required to maintain pluripotent/multipotent stem cells in both plants and animals. Thus, both kingdoms conserved or converged upon this fundamental feature of stem cell function. Here, we examine similarities and differences in Thr metabolism-dependent mechanisms supporting stem cell maintenance in these two kingdoms. We then consider common features of Thr metabolism in stem cell maintenance and predict and speculate that some knowledge about Thr metabolism and its role in stem cell function in one kingdom may apply to the other. Finally, we outline future research directions to explore these hypotheses.
Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling
Authors: Deng Jiamin , Wang Shangqi , Li Nan , Chen Xiaoyan , Wang Biying , Liu Han , Zhu Lei , Cong Wei , Xiao Jing , Liu Chao
Published: September 2021

The roles of bone morphogenetic protein (BMP) signaling in palatogenesis were well documented in the developing hard palate; however, little is known about how BMP signaling regulates the development of soft palate. In this study, we overexpressed Noggin transgene via Osr2-creKI allele to suppress BMP signaling in the developing soft palate. We found that BMP-Smad signaling was detected in the palatal muscles and surrounding mesenchyme. When BMP-Smad signaling was suppressed by the overexpressed Noggin, the soft palatal shelves were reduced in size with the hypoplastic muscles and the extroversive hypophosphatasia (HPP). The downregulated cell proliferation and survival in the Osr2-creKI;pMes-Noggin soft palates were suggested to result from the repressed Shh transcription and Gli1 activity, implicating that the BMP-Shh-Gli1 network played a similar role in soft palate development as in the hard palate. The downregulated Sox9, Tenascin-C (TnC), and Col1 expression in Osr2-creKI;pMes-Noggin soft palate indicated the impaired differentiation of the aponeurosis and tendons, which was suggested to result in the hypoplasia of palatal muscles. Intriguingly, in the Myf5-creKI;pMes-Noggin and the Myf5-creKI;Rosa26R-DTA soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the Scx, Tnc, and Co1 transcription was significantly repressed in the tenogenic mesenchyme of the Myf5-creKI;pMes-Noggin soft palate, the Sox9 expression, and the Tnc and Col1 transcription in aponeurosis mesenchyme were almost unaffected. It implicated that the fusion of soft palate was controlled by the mesenchymal clues at the tensor veli palatini (TVP) and levator veli palatini (LVP) levels, but by the myogenic components at the palatopharyngeus (PLP) level.
SPAAC Pulse-Chase: A Novel Click Chemistry-Based Method to Determine the Half-Life of Cellular Proteins
Authors: Morey Trevor M. , Esmaeili Mohammad Ali , Duennwald Martin L. , Rylett R. Jane
Published: September 2021

Assessing the stability and degradation of proteins is central to the study of cellular biological processes. Here, we describe a novel pulse-chase method to determine the half-life of cellular proteins that overcomes the limitations of other commonly used approaches. This method takes advantage of pulse-labeling of nascent proteins in living cells with the bioorthogonal amino acid L-azidohomoalanine (AHA) that is compatible with click chemistry-based modifications. We validate this method in both mammalian and yeast cells by assessing both over-expressed and endogenous proteins using various fluorescent and chemiluminescent click chemistry-compatible probes. Importantly, while cellular stress responses are induced to a limited extent following live-cell AHA pulse-labeling, we also show that this response does not result in changes in cell viability and growth. Moreover, this method is not compromised by the cytotoxicity evident in other commonly used protein half-life measurement methods and it does not require the use of radioactive amino acids. This new method thus presents a versatile, customizable, and valuable addition to the toolbox available to cell biologists to determine the stability of cellular proteins.
Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier
Authors: Allen Claire L. , Wolanska Katarzyna , Malhi Naseeb K. , Benest Andrew V. , Wood Mark E. , Amoaku Winfried , Torregrossa Roberta , Whiteman Matthew , Bates David O. , Whatmore Jacqueline L.
Published: September 2021

Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) are observed in diabetic patients and correlate with microvascular dysfunction. H2S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H2S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H2S donor NaGYY4137 in vitro. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. In vivo, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H2S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (p ≤ 0.001), and increased overall glycocalyx coverage (p ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (p ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (p < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups (p ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.
Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Intraepithelial Neoplasia in Chinese Women Living With HIV
Authors: Feng Min , Duan Rufei , Gao Yang , Zhang Han , Qiao Youlin , Li Qihan , Zhao Fanghui
Published: September 2021

Given that only a small percentage of human papillomavirus (HPV)-positive women develop cancer, HPV is necessary but insufficient for carcinogenesis. Mucosally transmitted viral cofactors appear to contribute to HPV-related cervical cancer, such as Epstein-Barr virus (EBV), but previous studies have shown inconsistent outcomes. The exact role of EBV in cervical cancer remains unclear, and more studies are needed to determine its involvement. In this study, we describe the prevalence of EBV and HPV coinfection in HIV-positive women and explore how abnormal host immune status induced by viral coinfections modulates epithelial gene expression. We found a significant correlation between EBV-HPV coinfection and the incidence of high-grade cervical intraepithelial neoplasia (CIN2+). RNA sequencing indicated that CIN tissues coinfected with EBV and HPV led to significant changes in the gene expression of epithelial differentiation and development compared to normal tissues with HPV infection alone. In particular, several differentially expressed genes (DEGs) are closely associated with cancer, such as CACNG4, which was confirmed to be upregulated at both the mRNA and protein levels. Therefore, these findings provide some evidence that EBV may act as a cofactor or mediator in HPV-related cervical cancer. Specific genes or proteins, such as CACNG4, may serve as biomarkers that can risk stratify patients based on pathological changes in the cervix.
How Low-Carbon Heat Requirements for Direct Air Capture of CO2 Can Enable the Expansion of Firm Low-Carbon Electricity Generation Resources
Authors: Slesinski Daniel , Litzelman Scott
Published: September 2021

A rapid build-out of direct air capture (DAC), deployed in order to mitigate climate change, will require significant amounts of both low-carbon thermal and electrical energy. Firm low-carbon power resources, including nuclear, geothermal, or natural gas with carbon capture, which also will become more highly valued as variable renewable energy penetration increases, would be able to provide both heat and electricity for DAC. In this study, we examined the techno-economic synergy between a hypothetical DAC plant in the year 2030 and a nuclear small modular reactor, and determined two avenues for which this relationship could benefit the nuclear plant. First, we demonstrated that, under certain assumptions, selling a portion of its energy to a DAC facility allows the nuclear plant to take in 21% less revenue from selling electricity to wholesale markets than its projected levelized cost, and still break even. Second, after estimating a potential revenue stream, we showed that an integration with DAC allows for the nuclear plant's capital costs to be up to 35% higher than what would be required if only selling electricity to wholesale markets. This could enable the nuclear plant to operate economically even in the face of variable and decreasing wholesale electricity prices, and also could offer developers more financial certainty when planning a new project. Ultimately, this study shows that the need for low-carbon energy for DAC plants might incentivize the development of advanced nuclear plants and firm low-carbon resources more broadly.
Circulating Syndecan-1 as a Predictor of Persistent Thrombocytopenia and Lethal Outcome: A Population Study of Patients With Suspected Sepsis Requiring Intensive Care
Authors: Hatanaka Kosaku , Ito Takashi , Madokoro Yutaro , Kamikokuryo Chinatsu , Niiyama Shuhei , Yamada Shingo , Maruyama Ikuro , Kakihana Yasuyuki
Published: September 2021

Background: Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection. Recent studies have suggested that endotheliopathy may be the common basis for multiple organ failure in sepsis. Under septic conditions, accumulation of proteases accelerates shedding of proteoglycans, such as syndecan-1, from the endothelial surface, resulting in augmented leukocyte adhesion to the vascular wall, enhanced vascular permeability, and intravascular coagulation. The purpose of this study was to determine the potential utility of syndecan-1 as a biomarker linking endotheliopathy to organ failure.

Methods: One hundred patients with suspected infections who were admitted to the intensive care unit (ICU) at Kagoshima University Hospital were consecutively enrolled in the study. Serum syndecan-1 levels were measured using an in-house enzyme-linked immunosorbent assay. The difference between serum syndecan-1 levels in 28-day survivors and non-survivors was analyzed by the Mann–Whitney U-test. Receiver-operating characteristics curve analysis with area under the curve calculation was used to quantify the predictive performance of serum syndecan-1 for 28-day mortality. The correlations between serum syndecan-1 and coagulation markers were analyzed by Spearman's rank correlation test.

Results: Serum syndecan-1 levels in non-survivors were significantly higher than those in survivors on Day 1 and Day 3 (P < 0.01). Among multiple organ failures, coagulation failure and renal failure were significantly correlated with serum syndecan-1. Spearman's rank correlation test indicated that serum syndecan-1 was weakly but significantly correlated with disseminated intravascular coagulation score (rho = 0.33, P < 0.01). Patients with serum syndecan-1 ≥21.4 ng/mL showed delayed recovery from thrombocytopenia relative to patients with serum syndecan-1 <21.4 ng/mL.

Conclusions: Elevated circulating syndecan-1 on the first day of ICU admission was associated with persistent thrombocytopenia and lethal outcome in patients with suspected sepsis.
Development and Validation of a Nomogram to Predict the 180-Day Readmission Risk for Chronic Heart Failure: A Multicenter Prospective Study
Authors: Gao Shanshan , Yin Gang , Xia Qing , Wu Guihai , Zhu Jinxiu , Lu Nan , Yan Jingyi , Tan Xuerui
Published: September 2021

Background: The existing prediction models lack the generalized applicability for chronic heart failure (CHF) readmission. We aimed to develop and validate a widely applicable nomogram for the prediction of 180-day readmission to the patients.

Methods: We prospectively enrolled 2,980 consecutive patients with CHF from two hospitals. A nomogram was created to predict 180-day readmission based on the selected variables. The patients were divided into three datasets for development, internal validation, and external validation (mean age: 74.2 ± 14.1, 73.8 ± 14.2, and 71.0 ± 11.7 years, respectively; sex: 50.2, 48.8, and 55.2% male, respectively). At baseline, 102 variables were submitted to the least absolute shrinkage and selection operator (Lasso) regression algorithm for variable selection. The selected variables were processed by the multivariable Cox proportional hazards regression modeling combined with univariate analysis and stepwise regression. The model was evaluated by the concordance index (C-index) and calibration plot. Finally, the nomogram was provided to visualize the results. The improvement in the regression model was calculated by the net reclassification index (NRI) (with tenfold cross-validation and 200 bootstraps).

Results: Among the selected 2,980 patients, 1,696 (56.9%) were readmitted within 180 days, and 1,502 (50.4%) were men. A nomogram was established by the results of Lasso regression, univariate analysis, stepwise regression and multivariate Cox regression, as well as variables with clinical significance. The values of the C-index were 0.75 [95% confidence interval (CI): 0.72–0.79], 0.75 [95% CI: 0.69–0.81], and 0.73 [95% CI: 0.64–0.83] for the development, internal validation, and external validation datasets, respectively. Calibration plots were provided for both the internal and external validation sets. Five variables including history of acute heart failure, emergency department visit, age, blood urea nitrogen level, and beta blocker usage were considered in the final prediction model. When adding variables involving hospital discharge way, alcohol taken and left bundle branch block, the calculated values of NRI demonstrated no significant improvements.

Conclusions: A nomogram for the prediction of 180-day readmission of patients with CHF was developed and validated based on five variables. The proposed methodology can improve the accurate prediction of patient readmission and have the wide applications for CHF.
The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage
Authors: Stancill Jennifer S. , Corbett John A.
Published: September 2021

Oxidative stress is hypothesized to play a role in pancreatic β-cell damage, potentially contributing to β-cell dysfunction and death in both type 1 and type 2 diabetes. Oxidative stress arises when naturally occurring reactive oxygen species (ROS) are produced at levels that overwhelm the antioxidant capacity of the cell. ROS, including superoxide and hydrogen peroxide, are primarily produced by electron leak during mitochondrial oxidative metabolism. Additionally, peroxynitrite, an oxidant generated by the reaction of superoxide and nitric oxide, may also cause β-cell damage during autoimmune destruction of these cells. β-cells are thought to be susceptible to oxidative damage based on reports that they express low levels of antioxidant enzymes compared to other tissues. Furthermore, markers of oxidative damage are observed in islets from diabetic rodent models and human patients. However, recent studies have demonstrated high expression of various isoforms of peroxiredoxins, thioredoxin, and thioredoxin reductase in β-cells and have provided experimental evidence supporting a role for these enzymes in promoting β-cell function and survival in response to a variety of oxidative stressors. This mini-review will focus on the mechanism by which thioredoxins and peroxiredoxins detoxify ROS and on the protective roles of these enzymes in β-cells. Additionally, we speculate about the role of this antioxidant system in promoting insulin secretion.
Identification of Key Candidate Genes and Chemical Perturbagens in Diabetic Kidney Disease Using Integrated Bioinformatics Analysis
Authors: Gao Zhuo , S Aishwarya , Li Xiao-mei , Li Xin-lun , Sui Li-na
Published: September 2021

Globally, nearly 40 percent of all diabetic patients develop serious diabetic kidney disease (DKD). The identification of the potential early-stage biomarkers and elucidation of their underlying molecular mechanisms in DKD are required. In this study, we performed integrated bioinformatics analysis on the expression profiles GSE111154, GSE30528 and GSE30529 associated with early diabetic nephropathy (EDN), glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. A total of 1,241, 318 and 280 differentially expressed genes (DEGs) were identified for GSE30258, GSE30529, and GSE111154 respectively. Subsequently, 280 upregulated and 27 downregulated DEGs shared between the three GSE datasets were identified. Further analysis of the gene expression levels conducted on the hub genes revealed SPARC (Secreted Protein Acidic And Cysteine Rich), POSTN (periostin), LUM (Lumican), KNG1 (Kininogen 1), FN1 (Fibronectin 1), VCAN (Versican) and PTPRO (Protein Tyrosine Phosphatase Receptor Type O) having potential roles in DKD progression. FN1, LUM and VCAN were identified as upregulated genes for GDKD whereas the downregulation of PTPRO was associated with all three diseases. Both POSTN and SPARC were identified as the overexpressed putative biomarkers whereas KNG1 was found as downregulated in TDKD. Additionally, we also identified two drugs, namely pidorubicine, a topoisomerase inhibitor (LINCS ID- BRD-K04548931) and Polo-like kinase inhibitor (LINCS ID- BRD-K41652870) having the validated role in reversing the differential gene expression patterns observed in the three GSE datasets used. Collectively, this study aids in the understanding of the molecular drivers, critical genes and pathways that underlie DKD initiation and progression.
Sulfur-Based Denitrification in Streambank Subsoils in a Headwater Catchment Underlain by Marine Sedimentary Rocks in Akita, Japan
Authors: Hayakawa Atsushi , Ota Hitoshi , Asano Ryoki , Murano Hirotatsu , Ishikawa Yuichi , Takahashi Tadashi
Published: September 2021

Sulfur-based denitrification may be a key biogeochemical nitrate (NO3−) removal process in sulfide-rich regions, but it is still poorly understood in natural terrestrial ecosystems. We examined sulfur-driven NO3− reduction using streambank soils in a headwater catchment underlain by marine sedimentary rock in Akita, Japan. In a catchment exhibiting higher sulfide content in streambed sediment, we sampled two adjacent streambank soils of streambank I (two layers) and of streambank II (eight layers). Anaerobic long-term incubation experiments (40 days, using soils of streambank I) and short-term incubation experiments (5 days, using soils of streambank II) were conducted to evaluate variations of N solutes (NO3−, NO2−, and NH4+), N gases (NO, N2O), and the bacterial flora. In both experiments, two treatment solutions containing NO3− (N treatment), and NO3− and S2O32− (N + S treatment) were prepared. In the N + S treatment of the long-term experiment, NO3− concentrations gradually decreased by 98%, with increases in the SO42−, NO2−, NO, and N2O concentrations and with not increase in the NH4+, indicating denitrification had occurred with a high probability. Temporal accumulation of NO2− was observed in the N + S treatment. The stoichiometric ratio of SO42− production and NO3− depletion rates indicated that denitrification using reduced sulfur occurred even without additional S, indicating inherent S also served as an electron donor for denitrification. In the short-term incubation experiment, S addition was significantly decreased NO3− concentrations and increased NO2−, NO, and N2O concentrations, especially in some subsoils with higher sulfide contents. Many denitrifying sulfur-oxidizing bacteria (Thiobacillus denitrificans and Sulfuricella denitrificans) were detected in both streambank I and II, which dominated up to 5% of the entire microbial population, suggesting that these bacteria are widespread in sulfide-rich soil layers in the catchment. We concluded that the catchment with abundant sulfides in the subsoil possessed the potential for sulfur-driven NO3− reduction, which could widely influence N cycling in and NO3− export from the headwater catchment.
Genetic Differentiation of Reintroduced Père David’s Deer (Elaphurus davidianus) Based on Population Genomics Analysis
Authors: Zhang Shumiao , Li Chao , Li Yiping , Chen Qi , Hu Defu , Cheng Zhibin , Wang Xiao , Shan Yunfang , Bai Jiade , Liu Gang
Published: September 2021

The reintroduction is an important conservation tool to restore a species in its historically distribution area, but the rate of reintroduction success varies across species or regions due to different reasons. Genetic evaluation is important to the conservation management of reintroduced species. Conservation concerns relate to genetic threats for species with a small population size or severely historically bottle-necked species, such as negative consequences associated with loss of genetic diversity and inbreeding. The last 40years have seen a rapid increasing of population size for Père David’s deer (Elaphurus davidianus), which originated from a limited founder population. However, the genetic structure of reintroduced Père David’s deer has not been investigated in terms of population genomics, and it is still not clear about the evolutionary history of Père David’s deer and to what extent the inbreeding level is. Conservation genomics methods were used to reconstruct the demographic history of Père David’s deer, evaluate genetic diversity, and characterize genetic structure among 18 individuals from the captive, free-ranging and wild populations. The results showed that 1,456,457 single nucleotide polymorphisms (SNPs) were obtained for Père David’s deer, and low levels of genome-wide genetic diversity were observed in Père David’s deer compared with Red deer (Cervus elaphus) and Sika deer (Cervus nippon). A moderate population genetic differentiation was detected among three populations of Père David’s deer, especially between the captive population in Beijing Père David’s deer park and the free-ranging population in Jiangsu Dafeng National Nature Reserve. The effective population size of Père David’s deer started to decline ~25.8ka, and the similar levels of three populations’ LD reflected the genetic impacts of long-term population bottlenecks in the Père David’s deer. The findings of this study could highlight the necessity of individual exchange between different facilities, and genetic management should generally be integrated into conservation planning with other management considerations.
Alpha-1 Antitrypsin Z Variant (AAT PI*Z) as a Risk Factor for Intrahepatic Cholestasis of Pregnancy
Authors: Kosinski Przemyslaw , Kedzia Malgorzata , Mostowska Adrianna , Gutaj Pawel , Lipa Michal , Wender-Ozegowska Ewa , Rozy Adriana , Chorostowska-Wynimko Joanna , Wielgos Miroslaw , Jezela-Stanek Aleksandra
Published: September 2021

Background: Intrahepatic cholestasis of pregnancy (ICP; prevalence 0.2–15.6%) is the most common pregnancy-related liver disorder. It may have serious consequences for a pregnancy, including increased risk of preterm delivery, meconium staining of amniotic fluid, fetal bradycardia, distress, and fetal demise. In cases of high bile acids (>100μmol/L), patients have 10-fold increase in the risk of stillbirth. Biophysical methods of fetal monitoring, such as cardiotocography, ultrasonography, or Doppler have been proven unreliable for risk prediction in the course of intrahepatic cholestasis. Therefore, we believe extensive research for more specific, especially early, markers should be carried out. By analogy with cholestasis in children with inherited alpha-1 antitrypsin deficiency (AATD), we hypothesized the SERPINA1 Z pathogenic variant might be related to a higher risk of cholestasis in pregnancy. This study aimed to investigate the most common AATD variants (Z and S SERPINA1 alleles) in a group of cholestatic pregnant women.

Results: The Z carrier frequency was calculated to be 6.8%, which is much higher compared to the general population [2.3%; the Chi-squared test with Yates correction is 6.8774 (p=0.008)].

Conclusion: Increased prevalence of SERPINA1 PI*Z variant in a group of women with intrahepatic cholestasis may suggest a possible genetic origin of a higher risk of intrahepatic cholestasis in pregnancy.
Associations Between Maternal Immunisation and Reduced Rates of Preterm Birth and Stillbirth: A Population Based Retrospective Cohort Study
Authors: Giles Michelle L. , Davey Mary-Ann , Wallace Euan M.
Published: September 2021

Stillbirth and preterm birth (PTB) remain two of the most important, unresolved challenges in modern pregnancy care. Approximately 10% of all births are preterm with nearly one million children dying each year due to PTB. It remains the most common cause of death among children under five years of age. The numbers for stillbirth are no less shocking with 2.6 million babies stillborn each year. With minimal impact on the rate of these adverse birth outcomes over the past decade there is an urgent need to identify more effective interventions to tackle these problems. In this retrospective cohort study, we used whole-of-population data, to determine if maternal immunization during pregnancy against influenza and/or pertussis, is associated with a lower risk of PTB, delivering a small-for-gestational age (SGA) infant, developing preeclampsia or stillbirth. Women with a singleton pregnancy at 28 or more weeks’ gestation delivering in Victoria, Australia from July 2015 to December 2018 were included in the analysis. Log-binomial regression was used to measure the relationship between vaccination during pregnancy against influenza and against pertussis, with preterm birth, SGA, preeclampsia and stillbirth. Variables included in the adjusted model were maternal age, body mass index, first or subsequent birth, maternal Indigenous status, socio-economic quintile, smoking, public or private maternity care and metropolitan or rural location of the hospital. Women who received influenza vaccine were 75% less likely to have a stillbirth (aRR 025; 95% CI 0.20, 0.31), and 31% less likely to birth <37 weeks (aRR 0.69; 95% CI 0.66, 0.72). Women who received pertussis vaccine were 77% less likely to have a stillbirth (aOR 0.23; 95% CI 0.18, 0.28) and 32% less likely to birth <37 weeks gestation (aRR 0.68; 95% CI 0.66, 0.71). Vaccination also reduced the odds of small for gestational age by 13% and reduced the odds of pre-eclampsia when restricted to primiparous women. This association was seen over four different influenza seasons and independent of the time of year suggesting that any protective effect on obstetric outcomes afforded by maternal vaccination may not be due to a pathogen-specific response but rather due to pathogen-agnostic immune-modulatory effects.
The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Leishmania amazonensis Interactions Lead to a Progressive Chronic Disease
Authors: Carneiro Matheus B. , Peters Nathan C.
Published: September 2021

Intracellular phagosomal pathogens represent a formidable challenge for innate immune cells, as, paradoxically, these phagocytic cells can act as both host cells that support pathogen replication and, when properly activated, are the critical cells that mediate pathogen elimination. Infection by parasites of theLeishmaniagenus provides an excellent model organism to investigate this complex host-pathogen interaction. In this review we focus on the dynamics ofLeishmania amazonensisinfection and the host innate immune response, including the impact of the adaptive immune response on phagocytic host cell recruitment and activation.L. amazonensisinfection represents an important public health problem in South America where, distinct from otherLeishmaniaparasites, it has been associated with all three clinical forms of leishmaniasis in humans: cutaneous, muco-cutaneous and visceral. Experimental observations demonstrate that most experimental mouse strains are susceptible toL. amazonensisinfection, including the C57BL/6 mouse, which is resistant to other species such asLeishmania major,Leishmania braziliensisandLeishmania infantum. In general, the CD4+T helper (Th)1/Th2 paradigm does not sufficiently explain the progressive chronic disease established byL. amazonensis, as strong cell-mediated Th1 immunity, or a lack of Th2 immunity, does not provide protection as would be predicted. Recent findings in which the balance between Th1/Th2 immunity was found to influence permissive host cell availabilityviarecruitment of inflammatory monocytes has also added to the complexity of the Th1/Th2 paradigm. In this review we discuss the roles played by innate cells starting from parasite recognition through to priming of the adaptive immune response. We highlight the relative importance of neutrophils, monocytes, dendritic cells and resident macrophages for the establishment and progressive nature of disease followingL. amazonensisinfection.
Resource Status and Effect of Long-Term Stock Enhancement of Large Yellow Croaker in China
Authors: Yuan Jigui , Lin Hungdu , Wu Lisheng , Zhuang Xuan , Ma Junkai , Kang Bin , Ding Shaoxiong
Published: September 2021

The large yellow croaker, Larimichthys crocea, was once the most abundant and economically important marine fish in China. Thus far, it has also been the most successful mariculture fish species in China. However, its wild stock severely declined in the 1970s because of overexploitation, and therefore hatchery release has been carried out for stock enhancement since 2000. As a migratory fish, large yellow croaker was divided into three geographical stocks according to ambiguous morphological and biological characteristics in early documents. To investigate the identity of wild large yellow croaker populations and assess the influence of hatchery supplementation on wild populations, a total of 2,785 cultured individuals and 591 wild individuals were collected from 91 hatcheries and six wild populations along the coast of mainland China and analyzed using two mitochondrial genes [cytochrome oxidase I (COI) and cytochrome b (Cyt b)] and one nuclear gene (RyR3). The higher haplotype diversity and moderate nucleotide diversity of wild large yellow croaker indicated that overexploitation, which caused a sharp decrease in biomass, did not lead to a loss of genetic diversity. According to phylogenetic construction and network analysis, the absence of a significant population structure pattern revealed a single panmictic population of wild large yellow croaker with exception of a population collected from the Sansha Bay, which showed high genetic relatedness to the cultured population, suggesting significant genetic effects resulting from stock enhancement. Overall, our study suggests no genetic differentiation in the entire wild population of large yellow croaker, which means that we have great flexibility in mixing and matching farmed and wild populations. However, since the result showed that domestication, the relaxation of purifying selection, increased genetic loads, and maladapted farmed fish will be at a selective disadvantage when cultured juveniles are released in the wild, the effectiveness of stock enhancement and the negative impact of hatchery-wild fish hybridization on the wild population must be carefully evaluated in future.
Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders
Authors: Liptak Robert , Gromova Barbora , Gardlik Roman
Published: September 2021

Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Moreover, FMT was proven to be effective in therapy of numerous animal models of disease. However, only a proportion of these disorders have been addressed in clinical studies using FMT. These include obesity, non-alcoholic fatty liver disease, cardiovascular inflammation and neurological disorders such as autism, depression and Parkinson's disease. Results from preclinical and clinical studies also outlined possible molecular mechanisms that contribute to alleviation of the disease. These range from increasing the circulating levels of microbial metabolites (trimethylamine N-oxide, lipopolysaccharide, short chain fatty acids) to stimulation of the enteric nervous system. Several methodological shortcomings are still to be addressed; however, positive results of the clinical studies indicate that further investigation of FMT as a therapeutic tool for non-gastrointestinal disorders can be expected in upcoming years.
Choriocapillaris Ischemia at the Leakage Point of Patients With Acute Central Serous Chorioretinopathy
Authors: Wang Zuofen , Xin Zhaoting , Yang Jun , Lu Huawen , Wang Haiying , Zhu Lin
Published: September 2021

Purpose: We aimed to determine ischemia of the choriocapillaris at the leakage point of patients with acute central serous chorioretinopathy (CSC) by optical coherence tomographic angiography (OCTA).

Methods: A retrospective study of 38 eyes of 38 acute CSC patients with spontaneous complete resolution of subretinal fluid (SRF) was conducted and patients were followed for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline. Best corrected visual acuity (BCVA) and OCTA were collected at baseline and at follow-up visits. An age- and refractive error-matched control group consisted of 40 eyes of 40 healthy people.

Results: The BCVA of patients significantly improved at 1 and 3 months. At baseline, all eyes showed a decreased choriocapillaris vessel density. The mean vessel density of superficial choroid (VDSC) at the leakage point area was 44.18 ± 9.27, which increased to 54.31 ± 9.70 at 1 month (p < 0.001) and to 55.19 ± 6.46 at 3 months (p < 0.001). The mean vessel density ratio was 0.90 ± 0.16 at baseline, which increased to 0.96 ± 0.15 at 1 month (p = 0.037) and to 0.97 ± 0.08 at 3 months (p = 0.016). The highest VDSC of patients was lower than that of normal control (p < 0.001).

Conclusions: The VDSC at the leakage point of acute CSC patients was significantly thinner and regularly increased with the recovery process, which suggested that ischemia might be one of the initiating factors in the pathogenesis of acute CSC.
Glucocorticoid Effects on Tissue Residing Immune Cells in Giant Cell Arteritis: Importance of GM-CSF
Authors: Wagner Annette D. , Wittkop Ulrike , Thalmann Jessica , Willmen Tina , Gödecke Vega , Hodam Justyna , Ronicke Simon , Zenke Martin
Published: September 2021

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis clinically characterized by a prompt response to glucocorticoid therapy. Dendritic cells (DCs) play a central role in the pathogenesis of the disease and are increased in temporal arteries from GCA patients. The aim of this study was to determine the effects of glucocorticoid therapy on granulomatous infiltrates and on peripheral DCs of GCA patients. Immunohistochemical staining of temporal artery specimens from 41 GCA patients revealed a rapid reduction of the number of DCs after initiation of glucocorticoid treatment. TUNEL staining was performed to quantify apoptotic S100+ DC, CD3+ T cells, and CD68+ macrophages in the granulomatous infiltrates. An increase of apoptotic cells up to 9 ± 2% after 4–5 days of glucocorticoid therapy and up to 27 ± 5% (p< 0.001, compared to earlier timepoints) after 6–10 days was detected. A decrease of CCL19 and CCL21 expression was observed after starting glucocorticoid therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also significantly decreased under glucocorticoid therapy. No GM-CSF expression was detected in the control specimens. Glucocorticoid therapy leads to a rapid, time-dependent reduction of DCs in temporal arteries from GCA patients and reduction of mediators for cell migration. Our data suggest GM-CSF as a novel therapeutic target of GCA.
Exploring Klebsiella pneumoniae in Healthy Poultry Reveals High Genetic Diversity, Good Biofilm-Forming Abilities and Higher Prevalence in Turkeys Than Broilers
Authors: Franklin-Alming Fiona V. , Kaspersen Håkon , Hetland Marit A. K. , Bakksjø Ragna-Johanne , Nesse Live L. , Leangapichart Thongpan , Löhr Iren H. , Telke Amar A. , Sunde Marianne
Published: September 2021

Klebsiella pneumoniae is a well-studied human pathogen for which antimicrobial resistant and hypervirulent clones have emerged globally. K. pneumoniae is also present in a variety of environmental niches, but currently there is a lack of knowledge on the occurrence and characteristics of K. pneumoniae from non-human sources. Certain environmental niches, e.g., animals, may be associated with high K. pneumoniae abundance, and these can constitute a reservoir for further transmission of strains and genetic elements. The aim of this study was to explore and characterize K. pneumoniae from healthy broilers and turkeys. A total of 511 cecal samples (broiler n = 356, turkey n = 155), included in the Norwegian monitoring program for antimicrobial resistance (AMR) in the veterinary sector (NORM-VET) in 2018, were screened for K. pneumoniae by culturing on SCAI agar. K. pneumoniae was detected in 207 (40.5%) samples. Among the broiler samples, 25.8% were positive for K. pneumoniae, in contrast to turkey with 74.2% positive samples (p < 0.01). Antibiotic susceptibility testing was performed, in addition to investigating biofilm production. Whole genome sequencing was performed on 203 K. pneumoniae isolates, and analysis was performed utilizing comparative genomics tools. The genomes grouped into 66 sequence types (STs), with ST35, ST4710 and ST37 being the most prevalent at 13.8%, 7.4%, and 5.4%, respectively. The overall AMR occurrence was low, with only 11.3% of the isolates showing both pheno- and genotypic resistance. Genes encoding aerobactin, salmochelin or yersiniabactin were detected in 47 (23.2%) genomes. Fifteen hypervirulent genomes belonging to ST4710 and isolated from turkey were identified. These all encoded the siderophore virulence loci iuc5 and iro5 on an IncF plasmid. Isolates from both poultry species displayed good biofilm-forming abilities with an average of OD595 0.69 and 0.64. To conclude, the occurrence of K. pneumoniae in turkey was significantly higher than in broiler, indicating that turkey might be an important zoonotic reservoir for K. pneumoniae compared to broilers. Furthermore, our results show a highly diverse K. pneumoniae population in poultry, low levels of antimicrobial resistance, good biofilm-forming abilities and a novel hypervirulent ST4710 clone circulating in the turkey population.