bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulasi Granul Effervescent Ekstrak Pandan Laut (Pandanus tectorius Parkinson ex Du Roi) Sebagai Analgetik
Authors: Sriarumtias Framesti Frisma
Published: January 2021

Sea pandanus plants are plants that are spread along the coast in Indonesia. Pandan sea fruit itself has never been used by the community, so it becomes waste on the beach. The purpose of this study was to make a formulation of effervescent granules from ethanolic extracts of sea pandanus (Pandanus tectorius) which has analgesic activity. The effervescent granule formula consists of ethanol extracts of sea pandanus, sodium bicarbonate, citric acid, tartaric acid, mannitol, lactose, PVP, aerosils and orange dyes. The difference of the three formulas are the ratio of the concentration of sodium bicarbonate which is 25%, 30% and 35%, respectively. The results show that the best formula is formula I, which fulfills the organoleptic test requirements, water content, rest angle, real specific gravity test, incompressible density test, compressibility, disperse time and pH. The analgesic activity test results using siegmund method known analgesic activity of formula I as the best formula with a dose of 125 mg / kg BW and aspirin as a comparison with a dose of 65 mg / kg body weight gives an anlgetic effect with protective power is 83.68%.
Uji Aktivitas Bakteri Keratinolitik Sebagai Penghasil Biosurfaktan
Authors: Rahayu Yayuk Putri , Prasetyo Healthy Aldriany
Published: January 2021

ABSTRAKBiosurfaktan banyak dimanfaatkan dalam bidang bioteknologi dan dapat diaplikasikan dalam berbagai industri seperti farmasi, obat-obatan, biomedis, kosmetik, oleokimia, produksi asam lemak dan turunannya, deterjen, penyamakan kulit, petrokimia dan minyak bumi. Penggunaan surfaktan dalam berbagai industri dapat menyebabkan masalah dalam penggunaannya karena dapat menyebabkan pencemaran lingkungan karena sifatnya yang sulit terurai (non biodegradable). Berdasarkan hal tersebut perlu mencari sumber surfaktan yang aman bagi lingkungan seperti biosurfaktan yang berasal dari mikroorganisme, salah satunya bakteri keratinolitik. Tujuan penelitian ini adalah untuk mencari sumber penghasil biosurfaktan dari isolat bakteri keratinolitik menggunakan teknik metode oil displacement dan emulsifikasi. Teknik pengujian aktivitas biosurfaktan dengan metode oil displacement dilakukan untuk mengukur zona perpindahan minyak untuk mendapatkan nilai oil displacement area (ODA), dan metode emulsifikasi dilakukan untuk menentukan nilai indeks emulsifikasi (IE24). Dari hasil pengujian biosurfaktan pada masing-masing isolat bakteri keratinolitik diperoleh nilai ODA sebesar 38.0 dan 15.0 mm dan EI24 sebesar 20 dan 15% untuk masing-masing isolat bakteri. Aktivitas biosurfaktan yang diperolah pada pengujian oil displacement seiring dengan hasil yang diperoleh pada pengujian emulsifikasi. Dari hasil penelitian ini dapat disimpulkan bahwa bakteri keratinolitik mampu menghasilkan biosurfaktan meskipun nilainya kecil.Kata Kunci: bakteri keratinolitik, biosurfaktan, indeks emulsifikasi, oil displacement.
Uji Toksisitas Akut dengan Menggunakan Metode Brine Shrimp Lethaly Test (BSLT) dan penetapan kadar Fenolik dan Flavonoid Ekstrak dan Fraksi Kulit Batang Kelor (Moringa oleifera)
Authors: Yamin Yamin , Sartinah Ari , Arba Muhammad , Candrayanti Gusti Ayu Made
Published: January 2021

Latar Belakang : Kelor dikenal sebagai The Miracle Tree atau pohon ajaib. Hal ini didukung dengan fakta bahwa kelor terbukti secara ilmiah merupakan sumber gizi berkhasiat obat(Tutik et al., 2018).  M. oleifera sudah banyak digunakan sebagai sumber makanan dan telah digunakan sebagai obat selama berabad-abad lamanya, diantaranya penyakit kulit, infeksi pernapasan, infeksi telinga dan gigi, hipertensi, diabetes, kanker, antiinflamasi, antioksidan, hiperglikemia dan makanan suplemen. Tujuan : untuk menentukan nilai toksisitas kulit batang kelor (Moringa oleifera) dengan menggunakan metode  Brine Shrimp Lethaly Test (BSLT). Metode : Serbuk kulit batang kelor diekstraksi dengan cara maserasi. Fraksi diperoleh dengan metode cair-cair. Sifat toksik diuji dengan menggunakan metode Brine Shrimp Lethaly Test (BSLT). Kadar fenolik dikur dengan menggunakan metode reagen Folin-Ciocalteau. Kadar flavonoid dianalisis dengan metode kolorimeter Aluminium klorida. Hasil : Ekstrak metanol menunjukkan nilai toksik yang kuat dibandingkan dengan fraksi n-heksan dan air dengan nilai toksisitas sebesar 153,394 ppm. Kadar fenolik dan flavonoid yang tertinggi terdapat pada ekstrak metanol dengan kadar sebesar  509,91 g EAG/100 g sampel untuk fenolik dan 536,11  gEK/100 g sampel  untuk flavonoid. Kesimpulan : Kulit batang kelor memiliki sifat toksik dengan ekstrak metanol paling toksik, sehingga bias ditelusuri lebih lanjut untuk mengetahui senyawa yang paling bersifat toksik
Profile of Fruit Consumption and Utilization of Jamu by Housewives in Cicanir and Jatipamor Villages in the Era of Germas and Fit with Jamu
Authors: Djunaedi Diah Dhianawaty , Heryaman Henhen - , Syamsunarno Mas Rizky Anggun Adipurna , Dahlan Anisah -
Published: January 2021

Healthy Lifestyle (Germas) and Fit with Jamu action (Bude Jamu) are the programs to improve health, which promote physical activities, consumption of fruits and vegetables, and the utilization of jamu. The figure of the mother in the family comes in the role of regulating a good diet for the family. In connection with these two programs, study was conducted to determine the profile of fruits consumption and utilization of jamu among housewives in Cicanir and Jatipamor villages, using the cross-sectional design with the number of respondents based on the number of minimum requirements in its activities. 150 Housewives were involved and given questions about the frequency of buying fruit, the favorite fruit, the habit of drinking jamu. The results were that most respondents bought fruit twice a week, their favorite fruits included orange, banana. People who drank jamu in Cicanir and Jatipamor were 40.79% and 25.86%, with the aim of disease prevention was 96.77% and treatment disease was 46.66%. Jamu gendong was the main source of jamu that was utilized, besides that the expertise in making jamu was still practiced and maintained by some respondents. In conclusions, fruit consumption in Cicanir and Jatipamor was quite good. Housewives in Cicanir and Jatipamor used jamu for the purpose of preventing and treating diseases. Jamu gendong was the most widely used source of jamu and the expertise in making jamu is still maintained. These all showed that the culture of Germas and Bude jamu have been applied in the lives of respondents.
HUBUNGAN PARITAS DENGAN KEJADIAN HIPEREMESIS GRAVIDARUM PADA IBU HAMIL
Authors: Paskana Kristina , Gusnidarsih Vevi
Published: January 2021

ABSTRAK

Di Indonesia terdapat 50-90 % kasus hiperemesis gravidarum yang di alami oleh ibu hamil. Berdasarkan survey awal dari data register Rumah Sakit Hassanuddin Damrah Manna Bengkulu Selatan tahun 2019 kejadian hiperemesis gravidarum tercatat 78 orang. Tujuan penelitian ini untuk mengetahui Hubungan Paritas Dengan Kejadian Hiperemesis Gravidarum Pada Ibu Hamil Di Rumah Sakit Hassanuddin Damrah. Penelitian ini dilakukan di Rumah Sakit Hassanuddin Damrah Manna Bengkulu Selatan pada tanggal 08 Juni sampai 13 Juni 2020. Penelitian ini merupakan penelitian deskriptif  korelasional dengan pendekatan cross sectional. Populasi dalam penelitian ini adalah seluruh ibu hamil usia â‰¤ 20  minggu yang dirawat di Rumah Sakit Hassanuddin Damrah Manna tahun 2019 yang berjumlah 200 orang. Pengumpulan data dalam penelitian ini menggunakan data sekunder yang di peroleh dari catatan medik Rumah Sakit Hassanuddin Damrah  Manna, kemudian data diolah secara univariat dan bivariat. Hasil penelitian 80,8% ibu hamil primigravida mengalami hipereemesis gravidarum, uji statistik chi-square didapatkan nilai p= 0,000 <0,05, yang artinya terdapat hubungan antara paritas ibu dengan kejadian hiperemesis gravidarum di Rumah Sakit Hassanuddin Damrah Manna Bengkulu Selatan.
Nutritive composition and essential elements evaluation of some leafy vegetables grown in Gubi Fadama Land, Bauchi, Nigeria
Authors: Yunus M M , Abdullahi L
Published: January 2021

Proximate analysis and some essential elements content of four leafy vegetable species namely: Brassica oleracea, Spinacia oleracea, Lactuca sativa and Hibiscus sabdariffa leaves were determined using standard analytical methods. These vegetables were widely consumed as food across Northeastern Nigeria. It is imperative to ascertain their nutritive values as they now form part of human diet for people in the area. Some of the results of the mean values ranged such as ash (2.33±0.75–6.03±1.23%), moisture (23.60±0.76–30.90±0.34%), lipid (0.45±0.00– 4.73±0.21%) and protein (2.62±0.10–3.38±0.013%). The mineral elements values ranged like potassium (145.47±4.50– 35.60±2.45mg/100g), sodium (74.97± 0.20– 389.85 ±0.02 mg/100g), calcium (9.87±0.13 –14.55  ±0.94mg/100g) iron (1.30±0.05–2.17±0.15 mg/100g), magnesium (0.030±0.00–0.047± 0.01mg/100g and manganese (0.004±0.00–0.015±0.00 mg/100g). The work suggested that the leaves investigated contained appreciable amounts of nutrients. Their consumption could augment the unavailable or rarely available nutrients in human body. Comparatively, they are good sources of K, Na, Ca and Fe, as well as fiber, moisture, and carbohydrates on the dietary menu recommendation. All the studied leaves have low lipid and protein content as well as copper, magnesium, and manganese.
A Comparative Analysis of Reactive Müller Glia Gene Expression After Light Damage and microRNA-Depleted Müller Glia—Focus on microRNAs
Authors: Kang Seoyoung , Larbi Daniel , Andrade Monica , Reardon Sara , Reh Thomas A. , Wohl Stefanie G.
Published: January 2021

Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include Gfap, Serpina3n, Ednrb and Cxcl10. (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with Maff , Egr2, Gadd45b, and Atf3 as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis.
Network and Pathway-Based Integrated Analysis Identified a Novel “rs28457673–miR-15/16/195/424/497 Family–IGF1R–MAPK Signaling Pathway” Axis Associated With Post-stroke Depression
Authors: Li Yan , Wang Zhi-chao , Zhu Ming-xi , Fan Gui-bo , Xu Gao-shuo , Zhao Tian-yang , Zhao A-yang , Ning Shang-wei , Qi Si-hua
Published: January 2021

Single-nucleotide polymorphisms (SNPs) of microRNA (miRNA) (miRSNP) are SNPs located on miRNA genes or miRNA target sites, which have been supposed to be involved in the development of central nervous system diseases by interfering with miRNA-mediated regulatory functions. However, the association of miRSNP with post-stroke depression (PSD) has not been well-investigated. In this study, we collected 54 PSD risk genes via manual literature-mining and integrated PSD-related risk pathways based on multiple public databases. Furthermore, we systematically screened candidate functional miRSNPs for PSD and integrated a miRSNP-based PSD-associated pathway network, which included 99 miRNAs that target 12 PSD risk pathways. We also reviewed the association between three risk pathways and PSD pathogenetic mechanism thoroughly. Combining literature mining and network analysis, our results proposed an underlying mechanism of “miRSNP → miRNA → risk gene → pathway” axis effects on PSD pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family) → IGF1R → hsa04010 (MAPK signaling pathway). Our studies revealed a functional role in genetic modifier at the system level in the pathogenesis of PSD, which might provide further information for the miRSNP studies in PSD.
Programmed Cell Senescence in the Mouse Developing Spinal Cord and Notochord
Authors: Domínguez-Bautista Jorge Antolio , Acevo-Rodríguez Pilar Sarah , Castro-Obregón Susana
Published: January 2021

Programmed cell senescence is a cellular process that seems to contribute to embryo development, in addition to cell proliferation, migration, differentiation and programmed cell death, and has been observed in evolutionary distant organisms such as mammals, amphibians, birds and fish. Programmed cell senescence is a phenotype similar to stress-induced cellular senescence, characterized by the expression of the cell cycle inhibitors p21CIP1/WAF and p16INK4A, increased activity of a lysosomal enzyme with beta-galactosidase activity (coined senescence-associated beta-galactosidase) and secretion of growth factors, interleukins, chemokines, metalloproteases, etc., collectively known as a senescent-associated secretory phenotype that instructs surrounding tissue. How wide is the distribution of programmed cell senescence during mouse development and its specific mechanisms to shape the embryo are still poorly understood. Here, we investigated whether markers of programmed cell senescence are found in the developing mouse spinal cord and notochord. We found discrete areas and developmental windows with high senescence-associated beta galactosidase in both spinal cord and notochord, which was reduced in mice embryos developed ex-utero in the presence of the senolytic ABT-263. Expression of p21CIP1/WAF was documented in epithelial cells of the spinal cord and the notochord, while p16INK4A was observed in motoneurons. Treatment with the senolytic ABT-263 decreased the number of motoneurons, supporting their senescent phenotype. Our data suggest that a subpopulation of motoneurons in the developing spinal cord, as well as some notochord cells undergo programmed cell senescence.
Experimental and Modeling Investigations of Miniaturization in InGaN/GaN Light-Emitting Diodes and Performance Enhancement by Micro-Wall Architecture
Authors: Zhang Yiping , Lu Shunpeng , Qiu Ying , Wu Jing , Zhang Menglong , Luo Dongxiang
Published: January 2021

The recent technological trends toward miniaturization in lighting and display devices are accelerating the requirement for high-performance and small-scale GaN-based light-emitting diodes (LEDs). In this work, the effect of mesa size-reduction in the InGaN/GaN LEDs is systematically investigated in two lateral dimensions (x- and y-directions: parallel to and perpendicular to the line where p-n directions are) both experimentally and numerically. The role of the lateral size-reduction in the x- and y-directions in improving LED performance is separately identified through experimental and modeling investigations. The narrowed dimension in the x-direction is found to cause and dominate the alleviated current crowding phenomenon, while the size-reduction in the y-direction has a minor influence on that. The size-reduction in the y-orientation induces an increased ratio of perimeter-to-area in miniaturized LED devices, which leads to improved thermal dissipation and light extraction through the sidewalls. The grown and fabricated LED devices with varied dimensions further support this explanation. Then the effect of size-reduction on the LED performance is summarized. Moreover, three-micro-walls LED architecture is proposed and demonstrated to further promote light extraction and reduce the generation of the Joule heat. The findings in this work provide instructive guidelines and insights on device miniaturization, especially for micro-LED devices.
GPER and Testicular Germ Cell Cancer
Authors: Chevalier Nicolas , Hinault Charlotte , Clavel Stephan , Paul-Bellon Rachel , Fenichel Patrick
Published: January 2021

The G protein-coupled estrogen receptor (GPER), also known as GPR30, is a widely conserved 7-transmembrane-domain protein which has been identified as a novel 17β-estradiol-binding protein that is structurally distinct from the classic oestrogen receptors (ERα and ERβ). There are still conflicting data regarding the exact role and the natural ligand of GPER/GPR30 in reproductive tracts as both male and female knock-out mice are fertile and have no abnormalities of reproductive organs. Testicular germ cell cancers (TGCCs) are the most common malignancy in young males and the most frequent cause of death from solid tumors in this age group. Clinical and experimental studies suggested that estrogens participate in the physiological and pathological control of male germ cell proliferation. In human seminoma cell line, while 17β-estradiol (E2) inhibits in vitro cell proliferation through an ERβ-dependent mechanism, an impermeable E2 conjugate (E2 coupled to BSA), in vitro cell proliferation is stimulated by activating ERK1/2 and protein kinase A through a membrane GPCR that we further identified as GPER/GPR30. The same effect was observed with low but environmentally relevant doses of BPA, an estrogenic endocrine disrupting compound. Furthermore, GPER/GPR30 is specifically overexpressed in seminomas but not in non-seminomas and this overexpression is correlated with an ERβ-downregulation. This GPER/GPR30 overexpression could be linked to some genetic variations, as single nucleotide polymorphisms, which was also reported in other hormone-dependent cancers. We will review here the implication of GPER/GPR30 in TGCCs pathophysiology and the arguments to consider GPER/GPR30 as a potential therapeutic target in humans.
Nexus Between Crop Residue Burning, Bioeconomy and Sustainable Development Goals Over North-Western India
Authors: Venkatramanan V. , Shah Shachi , Rai Ashutosh Kumar , Prasad Ram
Published: January 2021

The crop residue burning in India particularly North-western India is responsible for air pollution episodes and public health concerns; greenhouse gases emissions and radiation imbalance; and declining soil organic matter and soil productivity. The objectives of this paper are to estimate the crop residue burning and emissions from crop residue burning, to recommend interventions in crop residue management and to propose a crop residue management-bioeconomy model incorporating strategies to sustainably manage the crop residues through interventions that enable waste valorization, food and nutritional security, farmers’ livelihood and sustainable agricultural production system. A national inventory on crop residue burning including the pollutant species was prepared using the IPCC methodology. The crop types included for the estimation are cereals, pulses, oilseeds, sugarcane, cotton, jute and Mesta. The total amount of crop residues generated and burned for the year 2017–18 was estimated at 516 million tonnes and 116 million tonnes respectively. It is estimated that 116.3 Tg of crop residues burning released about 176.1 Tg of CO2, 10 Tg of CO, 313.9 Gg of CH4, 8.14 Gg of N2O, 151.14 Gg of NH3, 813.8 Gg of NMVOC, 453.4 Gg of PM2.5, and 935.9 Gg of PM10. The emission estimates can be a proxy to prepare the national level inventory of air pollutant species from crop residue burning. The crop residue management (CRM) demands a transition from the traditional zone of CRM to bioeconomy zone of CRM, wherein the interventions aim at the sustainability of agroecosystem. The proposed bioeconomy model has a four-pronged strategy that includes smart agriculture practices, waste bioeconomy involving aspirational principles of bioeconomy, capacity building of stakeholders’ and proactive government policy. Sustainable agricultural bioeconomy provides ample opportunities to reduce crop residue burning, increase farmers’ livelihood and decarbonize the agricultural production. India’s efforts and policies can provide lessons for other agricultural regions having similar environmental constraints.
Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer
Authors: Zhang Lili , Zhang Wei , Li Hexin , Tang Xiaokun , Xu Siyuan , Wu Meng , Wan Li , Su Fei , Zhang Yaqun
Published: January 2021

Prostate cancer (PCa) is the most common malignant tumor in men, and its incidence increases with age. Serum prostate-specific antigen and tissue biopsy remain the standard for diagnosis of suspected PCa. However, these clinical indicators may lead to aggressive overtreatment in patients who have been treated sufficiently with active surveillance. Circular RNAs (circRNAs) have been recently recognized as a new type of regulatory RNA that is not easily degraded by RNases and other exonucleases because of their covalent closed cyclic structure. Thus, we utilized high-throughput sequencing data and bioinformatics analysis to identify specifically expressed circRNAs in PCa and filtered out five specific circRNAs for further analysis—hsa_circ_0006410, hsa_circ_0003970, hsa_circ_0006754, hsa_circ_0005848, and a novel circRNA, hsa_circ_AKAP7. We constructed a circRNA-miRNA regulatory network and used miRNA and differentially expressed mRNA interactions to predict the function of the selected circRNAs. Furthermore, survival analysis of their cognate genes and PCR verification of these five circRNAs revealed that they are closely related to well-known PCa pathways such as the MAPK signaling pathway, P53 pathway, androgen receptor signaling pathway, cell cycle, hormone-mediated signaling pathway, and cellular lipid metabolic process. By understanding the related metabolism of circRNAs, these circRNAs could act as metabolic biomarkers, and monitoring their levels could help diagnose PCa. Meanwhile, the exact regulatory mechanism for AR-related regulation in PCa is still unclear. The circRNAs we found can provide new solutions for research in this field.
Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure
Authors: Rueschenbaum Sabrina , Ciesek Sandra , Queck Alexander , Widera Marek , Schwarzkopf Katharina , Brüne Bernhard , Welsch Christoph , Wedemeyer Heiner , Zeuzem Stefan , Weigert Andreas , Lange Christian M.
Published: January 2021

Introduction

Acute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system during the progression of liver cirrhosis to ACLF. Patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping was performed using high dimensional flow cytometry. Replication of Torque teno (TT) virus was quantified as a marker of immunosuppression. High frequencies of detectable TT virus were observed already in patients with compensated/stable decompensated liver cirrhosis compared to healthy controls (>50% vs. 19%), suggesting relatively early occurrence of immunosuppression in cirrhosis. In line, profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF. On a functional basis, the capacity of CD4+ and CD8+ T cells to produce pro-inflammatory cytokines upon stimulation was strongly diminished in patients with acute decompensation of liver cirrhosis and ACLF.

Conclusion

Impaired innate and—in particular—adaptive cellular immunity occurs relatively early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis.
Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment
Authors: Tiwari Drishti , Gupta Pawan
Published: January 2021

The escalation in living standards and adoption of ‘Western lifestyle’ has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.
Are Patients With Autoimmune Cytopenias at Higher Risk of COVID-19 Pneumonia? The Experience of a Reference Center in Northern Italy and Review of the Literature
Authors: Barcellini Wilma , Giannotta Juri Alessandro , Fattizzo Bruno
Published: January 2021

During COVID-19 pandemic the care of onco-hematologic and autoimmune patients has raised the question whether they are at higher risk of infection and/or worse outcome. Here, we describe the clinical course of COVID-19 pneumonia in patients with autoimmune cytopenias (AIC) regularly followed at a reference center in Northern Italy. The study period started from COVID-19 outbreak (February 22, 2020) until the time of writing. Moreover, we provide a review of the literature, showing that most cases reported so far are AIC developed during or secondary to COVID-19 infection. At variance, data about AIC pre-existing to COVID infection are scanty. The 4 patients here described (2 autoimmune hemolytic anemias, AIHA, 1 Evans syndrome, and 1 immune thrombocytopenia) with COVID-19 pneumonia belong to a large cohort of 500 AIC patients, making this study nearly population-based. The observed frequency (4/501; 0.7%) is only slightly superior to that of the general population admitted to hospital/intensive care unit (0.28/0.03%, respectively) in Lombardy in the same period of observation. All cases occurred between March 21 and 25, whilst no more AIC were recorded later on. Although different in intensity of care needed, all patients recovered from COVID-19 pneumonia, with apparently no detrimental effect of previous/current immunomodulatory treatments. AIHA relapse occurred in two patients, but promptly responded to therapy. With limitations due to sample size, these results suggest a favorable outcome and a lower-than-expected incidence of COVID-19 pneumonia in patients with previously diagnosed AIC, and allow speculating that immunomodulatory drugs used for AIC may play a beneficial rather than a harmful effect on COVID-19 infection.
Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency—Features of CT and 18F-FDG Positron Emission Tomography/CT in Clinically Progressive Disease
Authors: Fraz Mai Sasaki Aanensen , Moe Natasha , Revheim Mona-Elisabeth , Stavrinou Maria L. , Durheim Michael T. , Nordøy Ingvild , Macpherson Magnhild Eide , Aukrust Pål , Jørgensen Silje Fjellgård , Aaløkken Trond Mogens , Fevang Børre
Published: January 2021

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO.

Conclusion

Patients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.
The Choroid Plexus Is Permissive for a Preactivated Antigen-Experienced Memory B-Cell Subset in Multiple Sclerosis
Authors: Haas Jürgen , Rudolph Henriette , Costa Leonardo , Faller Simon , Libicher Saskia , Würthwein Cornelia , Jarius Sven , Ishikawa Hiroshi , Stump-Guthier Carolin , Tenenbaum Tobias , Schwerk Christian , Schroten Horst , Wildemann Brigitte
Published: January 2021

The role of B cells in multiple sclerosis (MS) is increasingly recognized. B cells undergo compartmentalized redistribution in blood and cerebrospinal fluid (CSF) during active MS, whereby memory B cells accumulate in the CSF. While B-cell trafficking across the blood–brain barrier has been intensely investigated, cellular diapedesis through the blood–CSF barrier (BCSFB) is incompletely understood. To investigate how B cells interact with the choroid plexus to transmigrate into the CSF we isolated circulating B cells from healthy donors (HC) and MS patients, utilized an inverted cell culture filter system of human choroid plexus papilloma (HIBCPP) cells to determine transmigration rates of B-cell subsets, immunofluorescence, and electron microscopy to analyze migration routes, and qRT-PCR to determine cytokines/chemokines mediating B-cell diapedesis. We also screened the transcriptome of intrathecal B cells from MS patients. We found, that spontaneous transmigration of HC- and MS-derived B cells was scant, yet increased significantly in response to B-cell specific chemokines CXCL-12/CXCL-13, was further boosted upon pre-activation and occurred via paracellular and transcellular pathways. Migrating cells exhibited upregulation of several genes involved in B-cell activation/migration and enhanced expression of chemokine receptors CXCR4/CXCR5, and were predominantly of isotype class switched memory phenotype. This antigen-experienced migratory subset displayed more pronounced chemotactic activities in MS than in HC and was retrieved in intrathecal B cells from patients with active MS. Trafficking of class-switched memory B cells was downscaled in a small cohort of natalizumab-exposed MS patients and the proportions of these phenotypes were reduced in peripheral blood yet were enriched intrathecally in patients who experienced recurrence of disease activity after withdrawal of natalizumab. Our findings highlight the relevance of the BCSFB as important gate for the entry of potentially harmful activated B cells into the CSF.
CU06-1004-Induced Vascular Normalization Improves Immunotherapy by Modulating Tumor Microenvironment via Cytotoxic T Cells
Authors: Park Songyi , Oh Ji Hoon , Park Dong Jin , Zhang Haiying , Noh Minyoung , Kim Yeomyung , Kim Ye-Seul , Kim Hyejeong , Kim Young-Myeong , Ha Sang-Jun , Kwon Young-Guen
Published: January 2021

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, the usage of a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types of cancer. Especially, vascular abnormal structures of which deter delivery route by leakage and cause the poor perfusion were considered to be environment unfavorable to T cells and immune checkpoint blockade (ICB) delivery within the tumor microenvironment (TME). Herein, we report stabilization of tumor blood vessels by endothelial dysfunctional blocker CU06-1004, which modified the TME and showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged the survival of tumor-bearing mice by decreasing tumor growth. T-cell infiltration increased in the tumors of the combination group, with cytotoxic CD8+ T cell activity within the tumor parenchyma upregulated compared with anti-PD-1 monotherapy. Tumor inhibition was associated with reduced hypoxia and reduced vessel density in the central region of the tumor. These effects correlated significantly with enhanced expression of IFN gamma and PD-L1 in tumors. Taken together, our findings suggest that CU06-1004 is a potential candidate drug capable of improving therapeutic efficacy of anti-PD-1 through beneficial changes in the TME.
Comparative Virulence and Genomic Analysis of Streptococcus suis Isolates
Authors: Nicholson Tracy L. , Waack Ursula , Anderson Tavis K. , Bayles Darrell O. , Zaia Sam R. , Goertz Isaiah , Eppinger Mark , Hau Samantha J. , Brockmeier Susan L. , Shore Sarah M.
Published: January 2021

Streptococcus suis is a zoonotic bacterial swine pathogen causing substantial economic and health burdens to the pork industry. Mechanisms used by S. suis to colonize and cause disease remain unknown and vaccines and/or intervention strategies currently do not exist. Studies addressing virulence mechanisms used by S. suis have been complicated because different isolates can cause a spectrum of disease outcomes ranging from lethal systemic disease to asymptomatic carriage. The objectives of this study were to evaluate the virulence capacity of nine United States S. suis isolates following intranasal challenge in swine and then perform comparative genomic analyses to identify genomic attributes associated with swine-virulent phenotypes. No correlation was found between the capacity to cause disease in swine and the functional characteristics of genome size, serotype, sequence type (ST), or in vitro virulence-associated phenotypes. A search for orthologs found in highly virulent isolates and not found in non-virulent isolates revealed numerous predicted protein coding sequences specific to each category. While none of these predicted protein coding sequences have been previously characterized as potential virulence factors, this analysis does provide a reliable one-to-one assignment of specific genes of interest that could prove useful in future allelic replacement and/or functional genomic studies. Collectively, this report provides a framework for future allelic replacement and/or functional genomic studies investigating genetic characteristics underlying the spectrum of disease outcomes caused by S. suis isolates.
Effect of Ethanol Vapor Treatment on the Growth of Alternaria alternata and Botrytis cinerea and Defense-Related Enzymes of Fungi-Inoculated Blueberry During Storage
Authors: Ji Yaru , Hu Wenzhong , Liao Jia , Xiu Zhilong , Jiang Aili , Yang Xiaozhe , Guan Yuge , Feng Ke , Saren Gaowa
Published: January 2021

The aim of the present study was to investigate the effects of ethanol vapor on the inhibition of Alternaria alternata and Botrytis cinerea in postharvest blueberry and the induction of defense-related enzymes (DREs) activities in fungi-inoculated blueberries stored at 0±0.5°C for 16days. Results indicated that ethanol vapor markedly inhibited the mycelial growth of A. alternata and B. cinerea in a dose-dependent manner, with inhibition rates of 9.1% (250μlL−1), 36.4% (500μlL−1), and 5.5% (1,000μlL−1) on A. alternata and 14.2% (250μlL−1), 44.7% (500μlL−1), and 76.6% (1,000μlL−1) on B. cinerea, respectively. Meanwhile, ethanol vapor also enhanced the activities of DREs in fungi-inoculated blueberries, including β-1,3-glucanase (GLU), chitinase (CHI), phenylalnine ammonialyase (PAL), peroxidase (POD), and polyphenol oxidase (PPO). In particular, 500μlL−1 ethanol vapor increased the activities of DREs by 84.7% (GLU), 88.0% (CHI), 37.9% (PAL), 85.5% (POD), and 247.0% (PPO) in A. alternata-inoculated blueberries and 103.8% (GLU), 271.1% (CHI), 41.1% (PAL), 148.3% (POD), and 74.4% (PPO) in B. cinerea-inoculated blueberries, respectively. But, the activity of PPO was decreased by 55.2 and 31.9% in 500μlL−1 ethanol-treated blueberries inoculated with A. alternata and B. cinerea, respectively, after 8days of storage. Moreover, the surface structure and ultrastructure of 500μlL−1 ethanol-treated blueberry fruit cells were more integrated than those of other treatments. The findings of the present study suggest that ethanol could be used as an activator of defense responses in blueberry against Alternaria and Botrytis rots, by activating DREs, having practical application value in the preservation of postharvest fruit and vegetables.
Reverse Engineering and Robotics as Tools for Analyzing Neural Circuits
Authors: Pisokas Ioannis
Published: January 2021

Understanding neuronal circuits that have evolved over millions of years to control adaptive behavior may provide us with alternative solutions to problems in robotics. Recently developed genetic tools allow us to study the connectivity and function of the insect nervous system at the single neuron level. However, neuronal circuits are complex, so the question remains, can we unravel the complex neuronal connectivity to understand the principles of the computations it embodies? Here, I illustrate the plausibility of incorporating reverse engineering to analyze part of the central complex, an insect brain structure essential for navigation behaviors such as maintaining a specific compass heading and path integration. I demonstrate that the combination of reverse engineering with simulations allows the study of both the structure and function of the underlying circuit, an approach that augments our understanding of both the computation performed by the neuronal circuit and the role of its components.
Adaptive Locomotion Control of a Hexapod Robot via Bio-Inspired Learning
Authors: Ouyang Wenjuan , Chi Haozhen , Pang Jiangnan , Liang Wenyu , Ren Qinyuan
Published: January 2021

In this paper, an adaptive locomotion control approach for a hexapod robot is proposed. Inspired from biological neuro control systems, a 3D two-layer artificial center pattern generator (CPG) network is adopted to generate the locomotion of the robot. The first layer of the CPG is responsible for generating several basic locomotion patterns and the functional configuration of this layer is determined through kinematics analysis. The second layer of the CPG controls the limb behavior of the robot to adapt to environment change in a specific locomotion pattern. To enable the adaptability of the limb behavior controller, a reinforcement learning (RL)-based approach is employed to tune the CPG parameters. Owing to symmetrical structure of the robot, only two parameters need to be learned iteratively. Thus, the proposed approach can be used in practice. Finally, both simulations and experiments are conducted to verify the effectiveness of the proposed control approach.
The Leukodystrophies HBSL and LBSL—Correlates and Distinctions
Authors: Muthiah Annapoorani , Housley Gary D. , Klugmann Matthias , Fröhlich Dominik
Published: January 2021

Aminoacyl-tRNA synthetases (ARSs) accurately charge tRNAs with their respective amino acids. As such, they are vital for the initiation of cytosolic and mitochondrial protein translation. These enzymes have become increasingly scrutinized in recent years for their role in neurodegenerative disorders caused by the mutations of ARS-encoding genes. This review focuses on two such genes—DARS1andDARS2—which encode cytosolic and mitochondrial aspartyl-tRNA synthetases, and the clinical conditions associated with mutations of these genes. We also describe attempts made at modeling these conditions in mice, which have both yielded important mechanistic insights.Leukoencephalopathy withbrainstem andspinal cord involvement andlactate elevation (LBSL) is a disease caused by a range of mutations in theDARS2gene, initially identified in 2003. Ten years later,hypomyelination withbrainstem andspinal cord involvement andleg spasticity (HBSL), caused by mutations of cytosolicDARS1, was discovered. Multiple parallels have been drawn between the two conditions. The Magnetic Resonance Imaging (MRI) patterns are strikingly similar, but still set these two conditions apart from other leukodystrophies. Clinically, both conditions are characterized by lower limb spasticity, often associated with other pyramidal signs. However, perhaps due to earlier detection, a wider range of symptoms, including peripheral neuropathy, as well as visual and hearing changes have been described in LBSL patients. Both HBSL and LBSL are spectrum disorders lacking genotype to phenotype correlation. While the fatal phenotype ofDars1orDars2single gene deletion mouse mutants revealed that the two enzymes lack functional redundancy, further pursuit of disease modeling are required to shed light onto the underlying disease mechanism, and enable examination of experimental treatments, including gene therapies.
Where to Find Leucine in Food and How to Feed Elderly With Sarcopenia in Order to Counteract Loss of Muscle Mass: Practical Advice
Authors: Rondanelli Mariangela , Nichetti Mara , Peroni Gabriella , Faliva Milena Anna , Naso Maurizio , Gasparri Clara , Perna Simone , Oberto Letizia , Di Paolo Enrica , Riva Antonella , Petrangolini Giovanna , Guerreschi Giulia , Tartara Alice
Published: January 2021

The term sarcopenia refers to the loss of skeletal muscle mass and strength that generally occurs during aging. The interventions that have proved most effective in reducing the severity and preventing the worsening of sarcopenia include physical exercise, especially resistance, and the administration of dietary supplements in association with a targeted diet; nutritional intervention is the main therapeutic approach for elderly people, since they are very often sedentary (also due to possible disabilities). Among the various nutrients, high biological value proteins and leucine are of particular interest for their demonstrated effects on the health of skeletal muscle. The intake of food containing proteins and leucine during meals stimulates muscle protein synthesis. Lower blood levels of leucine were associated with lower values of the skeletal muscle index, grip strength and performance. The international guidelines recommended that a leucine intake of 3 g at three main meals together with 25–30 g of protein is the goal to be achieved to counteract loss of lean mass in elderly. Food composition databases rarely show the amounts of leucine contained in foods and therefore it becomes difficult to build a diet that follows these guidelines. A table was therefore created for the first time in the literature to collect all the foods richest in leucine, thanks to the union of the most important Italian food databases. Moreover, in order to implement a diet that follows the right recommendations, another tables shows nutritional composition of breakfast, lunch and dinner (that each provide 3 grams of leucine and 25 grams of protein) for seven days.
Effects of Ramadan and Non-ramadan Intermittent Fasting on Body Composition: A Systematic Review and Meta-Analysis
Authors: Correia Joana M. , Santos Inês , Pezarat-Correia Pedro , Silva Analiza M. , Mendonca Goncalo V.
Published: January 2021

Intermittent fasting (IF) has gained popularity for body-composition improvement purposes. The aim of this systematic review and meta-analysis was to summarize the effects of Ramadan vs. non-Ramadan IF on parameters of body composition. We conducted a comprehensive search of peer-reviewed articles in three electronic databases: PubMed, Scopus, and Web of Science (published until May 2020). Studies were selected if they included samples of adults (≥18 years), had an experimental or observational design, investigated any type of IF and included body composition outcomes. Meta-analytical procedures were conducted when feasible. Sixty-six articles met the eligibility criteria. We found that non-Ramadan IF is effective for decreasing body weight (−0.341 (95% CI [−0.584, −0.098], p = 0.006), body mass index (−0.699, 95% CI [−1.05, −0.347], p < 0.001), and absolute fat mass (−0.447, 95% CI [−0.673, −0.221], p < 0.001). When contrasting pre- post-intervention data on fat-free mass between treatments and controls, group-differences were non-significant (p > 0.05). Conversely, we observed a significant increase in fat-free mass when comparing pre- to post-intervention in a within design fashion (0.306, 95% CI [0.133, 0.48], p = 0.001). Finally, despite being accompanied by dehydration, Ramadan IF is effective in decreasing body weight (−0.353; 95% CI [−0.651, −0.054], p = 0.02) and relative fat mass (−0.533; 95% CI [−1.025, −0.04], p = 0.034). Ramadan IF seems to implicate some beneficial adaptations in weight management, although non-Ramadan IF appears to be more effective in improving overall body composition.