bluuebunny/crossref_metadata_2025 huggingface dataset:
Electoral System
Authors: Fernandes Jorge M.
Published: November 2022

This chapter examines the Portuguese electoral system. Firstly, it unpacks its institutional building blocks by examining districts, magnitude, and the electoral formula. Secondly, it examines the historical roots of the electoral system to understand the incentives that led constitution-makers to choose particular electoral rules and regulations. Next, the chapter turns to the consequences of the electoral system. On the one hand, it examines the impact of within-system district magnitude variation for representation. On the other hand, it looks at legislators’ behavioural incentives in light of the electoral system. More specifically, the localism puzzle, that is, why legislators choose to engage in home service in the absence of institutional incentives. Lastly, the chapter looks at the institutional reforms (or lack thereof) of the Portuguese electoral system. The conclusion examines three lessons drawn from the impact of the electoral system on representation and democracy in Portugal.
Citizens and Politics: Support and Engagement
Authors: Magalhães Pedro C.
Published: November 2022

This chapter examines patterns and trends in public support for political authorities and the democratic regime in Portugal, as well regarding political engagement over the last two decades. Past assessments of the Portuguese case, particularly those based on social-scientific survey data, suggested that high levels of dissatisfaction with political authorities and low levels of political engagement have coexisted with a broad commitment towards democracy and its norms. Looking at data from the last two decades, this diagnosis seems to require some qualification. In spite of the large negative impact of the 2010–2013 economic crisis on specific support, the last few years—which coincided with a period of some economic recovery and the geringonça [government]—showed remarkably high levels of support for political authorities, a recovery that stands out against other countries that were similarly affected by the crisis. Furthermore, although electoral turnout has continued to decline, other forms of political participation have thrived, producing a convergence with levels found in established European democracies. Finally, there are signs that the commitment of the Portuguese to liberal democracy as a regime is exhibiting new signs of ambivalence, to which the strong emphasis on economic egalitarianism in political culture—and the perceived meagre achievements of Portuguese democracy in that respect—seem to be contributing.
Interest Groups, Business Associations, and Unions
Authors: Lisi Marco , Loureiro João
Published: November 2022

Interest groups are commonly defined as organizations that aim to influence public policies without contesting elections or taking government positions. These actors play an important role in terms of political representation and the policy-making process. This chapter explores the different dimensions of interest group politics in Portugal, a topic that has been largely understudied especially when compared with other Western democracies. The chapter begins with a review of the system of interest intermediation, which aims to frame the Portuguese case from both a theoretical and historical perspective. Thereafter, the chapter focuses on economic groups, i.e. business associations and trade unions, and examines two key dimensions in particular, namely organizational features and mobilization strategies. Lastly, the chapter discusses recent developments and the challenges ahead.
Political Corruption in Portugal
Authors: de Sousa Luís , Coroado Susana
Published: November 2022

Anticorruption reforms in Portugal have been a central feature both during and after the democratic transition, as part of governmental efforts to modernize the public administration and leverage economic development. However, political corruption only began to be addressed in the 1990s, due to political scandals and media salience, pressure from public opinion and international organizations during times of economic hardship. Both the executive and the legislative powers have responded to such pressures by approving successive anticorruption legislative packages. Yet these reforms lacked supporting evidence, strategic objectives, multi-stakeholder involvement, expert input, and benchmarking of best practices, and therefore failed to match citizens’ expectations of political integrity.
Portugal and Africa
Authors: Soares de Oliveira Ricardo
Published: November 2022

This chapter studies the set of post-colonial relationships between Portugal and its five former African colonies. It argues that they are fundamentally shaped by the nature of Portuguese colonialism, the patterns of decolonization, and the evolution of societies and political systems over the four decades that elapsed. The chapter first surveys the unsettled character of initial post-colonial relations in the context of the global Cold War, before analysing the key period in the early 1990s during which the relationship was reconfigured. It proceeds to discuss the major institutions and social groups shaping African relations in contemporary Portugal. Finally, the chapter explores the unbalancing of the post-colonial relationship in the context of Portugal’s post-2008 economic turmoil, highlighting the resultant increase in criticism towards established patterns of post-colonial relations with African states and the extent to which this is now a somewhat contested and more closely scrutinized arena.
Security and Geostrategy
Authors: Oliveira Martins Bruno , Pinéu Daniel
Published: November 2022

This chapter analyses the main pillars of the dominant security and geostrategic thinking in Portugal in both their discursive and policy dimensions. We argue that the country’s security and defence policies are developed within a balance between classical alliances in the North Atlantic, a commitment to European integration, and a postcolonial strategic interest in Portuguese-speaking countries. The chapter reviews key literature on the topic, and positions Portuguese developments within broader international contexts, in particular NATO and the defence structures within the EU. The chapter also examines the evolution of Portugal’s security policies (beyond the classical matrix of a small power managing a balancing act between the Atlantic, European, and post-colonial dimensions), and what drives change in them, particularly by highlighting new topics of concern.
The Role of the Portuguese Parliament
Authors: Goes Eunice , Leston-Bandeira Cristina
Published: November 2022

This chapter charts the development of the Assembleia da República—(AR) [Assembly of the Portuguese Republic] since 1976 until the present and argues that the Portuguese parliament is now a mover and shaker in Portugal’s politics. To show how the AR became an assertive legislature, the chapter explains the different roles it performs in the Portuguese political system. As such, it explains its relationship with the executive, followed by a discussion of the role played by parliamentary party groups and parliamentary committees. This section sets the stage for an explanation of how the Portuguese legislature influences the legislative agenda and scrutinizes the executive. The chapter also shows how the AR is reclaiming a more active role in the scrutiny of European legislation and is responding to the decline of public interest and trust in democratic institutions.
A Genealogy of Intersectionality
Authors: Houh Emily
Published: November 2022

This chapter traces the genealogy of intersectionality theory from its roots in diverse intellectual traditions including critical race theory (CRT), Black feminist thought, and Third World feminism, with a particular emphasis on CRT. It also identifies key substantive insights and characteristics of intersectionality theory and, in doing so, describes how these insights derive from both CRT and women of color–centered feminisms. The chapter concludes by discussing how different contemporary social justice movements—as exemplified by the Black Lives Matter movement—have put intersectionality theory into practice, and how it continues to anchor activist struggles in the face of fierce backlash forces.
Distributing a billion vaccines: COVAX successes, challenges, and opportunities
Authors: Budish Eric , Kettler Hannah , Kominers Scott Duke , Osland Erik , Prendergast Canice , Torkelson Andrew A
Published: November 2022

By January 2022, the COVAX international vaccine collaboration had allocated over a billion vaccines to over 140 countries. We describe and review the allocation process chosen, which reflected both an objective of equitably distributing vaccines across the world and the need to fund that mission. We show how vaccine supply limitations and constraints on some countries’ absorptive capacity have affected overall allocative outcomes. We also discuss market design approaches that were considered but not implemented, including the use of an exchange mechanism to better match countries’ vaccine allocations to their preferences, as well as a vaccine brokerage under which countries could sell excess vaccines to countries with ongoing need. Our analysis addresses some criticisms of COVAX, and offers suggestions for agencies organizing global vaccine cooperation for future pandemics.
Distinct stimulus-dependent neutrophil dynamics revealed by real-time imaging of intestinal mucosa after acute injury
Authors: Azcutia Veronica , Kelm Matthias , Kim Seonyoung , Luissint Anny-Claude , Flemming Sven , Abernathy-Close Lisa , Young Vincent B , Nusrat Asma , Miller Mark J , Parkos Charles A
Published: November 2022

Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds. Similar numbers of PMNs infiltrated colonic mucosa after wounding in germ-free mice, suggesting microbiota-independent mechanisms. By contrast, acute mucosal injury secondary to either a treatment of mice with dextran sodium sulfate or an IL-10 receptor blockade model of colitis resulted in lamina propria infiltration with PMNs that were largely immotile. Biopsy wounding of colonic mucosa in DSS-treated mice did not result in enhanced PMN swarming however, intraluminal application of the neutrophil chemoattractant LTB4 under such conditions resulted in enhanced transepithelial migration of PMNs. Analyses of PMNs that had migrated into the colonic lumen revealed that the majority of PMNs were directly recruited from the circulation and not from the immotile pool in the mucosa. Decreased PMN motility parallels upregulation of the receptor CXCR4 and apoptosis. Similarly, increased expression of CXCR4 on human PMNs was observed in colonic biopsies from people with active ulcerative colitis. This new approach adds an important tool to investigate mechanisms regulating PMN migration across mucosa within the distal intestine and will provide new insights for developing future anti-inflammatory and pro-repair therapies.
Inertialess gyrating engines
Authors: Siches Jordi Ventura , Miangolarra Olga Movilla , Taghvaei Amirhossein , Chen Yongxin , Georgiou Tryphon T
Published: November 2022

A typical model for a gyrating engine consists of an inertial wheel powered by an energy source that generates an angle-dependent torque. Examples of such engines include a pendulum with an externally applied torque, Stirling engines, and the Brownian gyrating engine. Variations in the torque are averaged out by the inertia of the system to produce limit cycle oscillations. While torque generating mechanisms are also ubiquitous in the biological world, where they typically feed on chemical gradients, inertia is not a property that one naturally associates with such processes. In the present work, seeking ways to dispense of the need for inertial effects, we study an inertia-less concept where the combined effect of coupled torque-producing components averages out variations in the ambient potential and helps overcome dissipative forces to allow sustained operation for vanishingly small inertia. We exemplify this inertia-less concept through analysis of two of the aforementioned engines, the Stirling engine, and the Brownian gyrating engine. An analogous principle may be sought in biomolecular processes as well as in modern-day technological engines, where for the latter, the coupled torque-producing components reduce vibrations that stem from the variability of the generated torque.
Ko Kuei Chen: A Pioneer of Modern Pharmacological Research in China
Authors: Liu Huan , Liu Zhaoqi , Gong Xue , Cheng Hao
Published: November 2022

Ko Kuei Chen (陈克恢, 1898–1988) (Fig. 1) was a pharmacologist who ceaselessly strove for medical research all his life. He was a pioneer of modern pharmacological research in Chinese medicine (Qian, 2014).

He systematically studied the pharmacological action of ephedrine and published the first paper on this topic in the world. He discovered that injecting sodium nitrite and sodium thiosulfate intravenously could effectively treat acute cyanide poisoning (Chen et al., 1952). He isolated cinobufagin and cinobufotoxin from Ch’an Su, the dried venom of the Chinese toad. His research in pharmacology enriched the treasure trove of medicine. Ko Kuei Chen was a pioneer of pharmacology in Chinese medicine, and his research had epoch-making significance in the field. His pharmacological research on ephedrine set a milestone in the world medicine history.
The Social and Political Lives of Women in an Egalitarian Matricultural Society: The Case of Western Sahara
Authors: Tripp Aili Mari
Published: November 2022

Gender equality is generally discussed as a liberal goal within international discourse. But nonliberal conceptions of gender egalitarianism coexist with and interact with liberal understandings in many contemporary societies. This article offers analysis of a Muslim matricultural society in Western Sahara made up of the Sahrawi people, where domestic violence is rare, where gender egalitarianism is highly valued, and where women are encouraged to become politically and economically active. The article explores the meaning of female agency in a society with cultural norms that promote women’s autonomy, yet also in the context of a society more broadly constrained by a lack of self-determination due to external occupation. The study draws on interviews and focus groups in Dakhla and El Aaiún.
Performance of rabbit does and weaned kits fed a granulated diet supplemented with Desmodium or Panicum fodders
Authors: Koné Gningnini A , Good Margaret , Tiho Tagouèlbè , Konan Koffi M , Nguessan Konan R , Kouba Maryline
Published: November 2022

Rabbit production is increasing in developing countries and can play a crucial role in the fight against poverty. The current work assessed the effect on rabbit does’ reproduction and young kits’ growth when either Panicum maximum, common name Guinea grass, or Desmodium tortuosum, common name Beggarweed is included in their diet. Diets ReC and GrC (standard granulated diets) served as control diets, formulated for doe Reproduction and kit Growth respectively. The trial diets were diets RePan/GrPan (diet ReC/GrC supplemented with dry P. maximum) and diets ReDes/GrDes (diet ReC/GrC supplemented with dry D. tortuosum). Thirty-six primiparous local breed five-month old rabbit does were randomly allocated to each one of the three dietary treatments. After a 15-day dietary adaptation period, does were each bred to one of 12, related, breeding males. Does were then assigned to individual maternity cages maintaining the same dietary treatment for the ensuing 65 days of the trial (30 days of gestation + 35 days of suckling). Thus, there were a total of 12 replicates per treatment: diet ReC, diet RePan or diet ReDes. At weaning, 72 kits, from the three adult feed treatment groups, were, while maintaining the integrity of the feed group of their individual mothers, divided into 12 blocks with 6 weaned kits per block, with each block allocated one of the three diets. Thus, for each of the three diets there were four separate blocks, i.e., four replicates, each with six group-housed weaned kits that received a growth diet which contained the same supplement or not as their mother diet to which they had access prior to weaning; the control diet GrC (Composition slightly different from Diet ReC composition) and trial diets GrPan and GrDes over a 3-day transition phase were adapted to the weaned kits physiological state and fed for a total of 56 days. The results indicated that the use of D. tortuosum significantly improved (P < 0.05) litter size, milk quantity, and kit survival rate from birth to weaning as compared with both control and RePan diets. The study showed that after weaning, compared with control and GrPan diets, the use of D. tortuosum increased (P < 0.05) the growth performance of weaned kits, improved meat nutritional quality by reducing (P < 0.05) cholesterol concentration and increasing (P < 0.05) the n-3 fatty acid proportion, and also reduced the individual kit feed cost to slaughter weight.
Extraordinary Case: Unique Presentation of an Aggressive Epstein-Barr Virus–Positive Mucocutaneous Ulcer
Authors: Miyashiro Denis , Nico Marcello Menta S. , Ang Patrícia Lin , Coelho Siqueira Sheila Aparecida , Pereira Juliana , Sanches José Antonio , Lourenço Silvia Vanessa
Published: November 2022

Epstein-Barr virus–positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus–related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.
Homoarginine in health and disease
Authors: Tsikas Dimitrios
Published: November 2022

Purpose of review

Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid. It is enzymatically synthesized from L-arginine and L-lysine. Low hArg concentrations appear to be a risk factor in the renal and cardiovascular systems. This review discusses advances in-vitro and in-vivo experimental and clinical research on hArg in health and disease.

Recent findings

Recent studies indicate that low circulating and low urinary concentrations of hArg are associated with morbidity and worse outcome. Although the biological activities of hArg remain still unexplored, hArg supplementation is intensely investigated as a strategy to increase hArg concentration to reach normal levels in cases of low hArg concentrations. The greatest changes in circulating hArg concentrations are observed during pregnancy and after delivery. In healthy adults, a daily dose of 125 mg hArg seems to be optimum to normalize circulating levels. Short-term supplementation of inorganic nitrate enhances hArg biosynthesis in healthy young men. Apart from hArg supplementation, dietary L-arginine and L-citrulline appear to be a promising alternative.

Considerable progress has been made in recent years, but hArg remains still enigmatic. Further research is required to explore the biological activities of hArg. Supplementation of hArg or its precursors L-citrulline/L-arginine seem to be promising strategies to prevent and overcome altered hArg synthesis.
HIV Increases the Risk of Cigarette Smoke-Induced Emphysema Through MMP-9
Authors: Staitieh Bashar S. , Malik Simran , Auld Sara C. , Wigger Gregory W. , Fan Xian , Roth Andrew T. , Chatterjee Tanima , Arora Itika , Raju S. Vamsee , Heath Sonya , Aggrawal Saurabh
Published: November 2022

Background:

HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9.

Methods:

HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed to the HIV protein Tat, and MMP-9 levels were assessed by Western immunoblotting. MMP-9 protein expression and activity were assessed in AM from the HIV rat model by ELISA and cytoimmunofluoresence, respectively. Serum from human subjects with and without HIV and tobacco dependence was assessed for MMP-9 levels.

Results:

MMP-9 expression was significantly increased in rat alveolar macrophages after Tat exposure. HIV-1 transgenic rats developed emphysema while wild-type littermates did not. MMP-9 expression was also increased in the serum, BAL, and AM of HIV-1 transgenic rats after exposure to cigarette smoke compared with wild-type rats. In parallel, serum samples from HIV+ smokers had higher levels of MMP-9 than subjects without HIV and those who did not smoke.

Conclusion:

The combination of HIV and cigarette smoke increases MMP-9 expression in experimental rat HIV models and human subjects. HIV and cigarette smoke both induce alveolar oxidative stress and thereby increase MMP-9 activity.
The Molecular Human – A Roadmap of Molecular Interactions Linking Multiomics Networks with Disease Endpoints
Authors: Halama Anna , Zaghlool Shaza , Thareja Gaurav , Kader Sara , Muftha Wadha Al , Mook-Kanamori Marjonneke , Sarwath Hina , Mohamoud Yasmin Ali , Ameling Sabine , Baković Maja Pucic , Krumsiek Jan , Prehn Cornelia , Adamski Jerzy , Friedrich Nele , Völker Uwe , Wuhrer Manfred , Lauc Gordan , Najafi Hani , Malek Joel A , Graumann Johannes , Mook-Kanamori Dennis , Schmidt Frank , Suhre Karsten
Published: November 2022

In-depth multiomics phenotyping can provide a molecular understanding of complex physiological processes and their pathologies. Here, we report on the application of 18 diverse deep molecular phenotyping (omics-) technologies to urine, blood, and saliva samples from 391 participants of the multiethnic diabetes study QMDiab. We integrated quantitative readouts of 6,304 molecular traits with 1,221,345 genetic variants, methylation at 470,837 DNA CpG sites, and gene expression of 57,000 transcripts using between-platform mutual best correlations, within-platform partial correlations, and genome-, epigenome-, transcriptome-, and phenome-wide associations. The achieved molecular network covers over 34,000 statistically significant trait-trait links and illustrates “The Molecular Human”. We describe the variances explained by each omics layer in the phenotypes age, sex, BMI, and diabetes state, platform complementarity, and the inherent correlation structures of multiomics. Finally, we discuss biological aspects of the networks relevant to the molecular basis of complex disorders. We developed a web-based interface to “The Molecular Human”, which is freely accessible athttp://comics.metabolomix.comand allows dynamic interaction with the data.
Antiviral effect of candies containing persimmon-derived tannin against SARS-CoV-2 delta strain
Authors: Furukawa Ryutaro , Kitabatake Masahiro , Ouji-Sageshima Noriko , Tomita Dai , Kumamoto Makiko , Suzuki Yuki , Nakano Akiyo , Nakano Ryuichi , Matsumura Yoko , Kayano Shin-ichi , Yano Hisakazu , Tamaki Shinji , Ito Toshihiro
Published: November 2022

Inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the mouth has the potential to reduce the spread of coronavirus disease 2019 (COVID-19) because the virus is readily transmitted by dispersed saliva. Persimmon-derived tannin has strong antioxidant and antimicrobial activity owing to its strong adhesiveness to proteins, and it also exhibited antiviral effects against non-variant and alpha variant SARS-CoV-2 in our previous study. In this report, we first demonstrated the antiviral effects of persimmon-derived tannin against the delta variant of SARS-CoV-2in vitrovia the plaque assay method. We then examined the effects of candy containing persimmon-derived tannin. Our plaque assay results show that saliva samples provided by healthy volunteers while they were eating tannin-containing candy remarkably suppressed the virus titers of the SARS-CoV-2 delta variant. In addition, we found that the SARS-CoV-2 viral load in saliva from patients with COVID-19 that was collected immediately after they had eaten the tannin-containing candy was below the level of detection by PCR for SARS-CoV-2. These data suggest that adding persimmon-derived tannin to candy and holding such candy in the mouth is an effective method by which to inactivate the SARS-CoV-2 in saliva, and the application of this approach has potential for inhibiting the transmission of COVID-19.
A Sox17 downstream geneRasip1is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo
Authors: Melig Gerel , Nobuhisa Ikuo , Saito Kiyoka , Tsukahara Ryota , Itabashi Ayumi , Kanai Yoshiakira , Kanai-Azuma Masami , Osawa Mitsujiro , Oshima Motohiko , Iwama Atsushi , Taga Tetsuya
Published: November 2022

Background

During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta’s intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17, is expressed in IAHCs, and that, among them, CD45lowc-Kithighcells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity.

Methods

RNA-sequencing (RNA-seq) analysis was done to identify genes that are up- regulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study and firstly the whole-mount immunostaining was done. We conducted a luciferase reporter assay to identify the Sox17 binding site for Rasip1 gene induction. We also analyzed the cluster formation and the multi-lineage colony forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells.

Results

The increase of theRasip1expression level was observed in Sox17-positive CD45lowc-Kithighcells as compared with the Sox17-nonexpressing control. Also, the expression level of theRasip1gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Overexpression of Rasip1 in CD45lowc-Kithighcells led to a significant but transient increase in hematopoietic activity, while Rasip1 knock-down in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability.

Conclusions

Rasip1 knockdown in Sox17-transduced CD45lowc-Kithighcells displayed a significant decrease in the multi-lineage colony forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithighcells led to a significant but transient increase in the multi-lineage colony forming ability, suggesting the presence of a cooperating factor for sustained hematopoietic activity.
END-TO-END CLASSIFICATION OF CELL-CYCLE STAGES WITH CENTER-CELL FOCUS TRACKER USING RECURRENT NEURAL NETWORKS
Authors: Jose Abin , Roy Rijo , Eschweiler Dennis , Laube Ina , Azad Reza , Moreno-Andrés Daniel , Stegmaier Johannes
Published: November 2022

Cell division, or mitosis, guarantees the accurate inheritance of the genomic information kept in the cell nucleus. Malfunctions in this process cause a threat to the health and life of the organism, including cancer and other manifold diseases. It is therefore crucial to study in detail the cell-cycle in general and mitosis in particular. Consequently, a large number of manual and semi-automated time-lapse microscopy image analyses of mitosis have been carried out in recent years. In this paper, we propose a method for automatic detection of cell-cycle stages using a recurrent neural network (RNN). An end-to-end model with center-cell focus tracker loss, and classification loss is trained. The evaluation was conducted on two time-series datasets, with 6-stages and 3-stages of cell splitting labeled. The frame-to-frame accuracy was calculated and precision, recall, and F1-Score were measured for each cell-cycle stage. We also visualized the learned feature space. Image reconstruction from the center-cell focus module was performed which shows that the network was able to focus on the center-cell and classify it simultaneously. Our experiments validate the superior performance of the proposed network compared to a classifier baseline.
A gene silencing screen uncovers diverse tools for targeted gene repression in Arabidopsis
Authors: Wang Ming , Zhong Zhenhui , Gallego-Bartolomé Javier , Li Zheng , Feng Suhua , Kuo Peggy Hsuanyu , Kan Ryan L. , Lam Hoiyan , Richey John , Jami-Alahmadi Yasaman , Wohlschlegel James , Jacobsen Steven E.
Published: November 2022

DNA methylation has been utilized for target gene silencing in plants, however it’s not well-understood whether other silencing pathways can be also used to manipulate gene expression. Here we performed a gain of function screen for proteins that could silence a target gene when fused to an artificial zinc finger. We uncovered many proteins that suppressed gene expression either through the establishment of DNA methylation, or via DNA methylation-independent processes including histone H3K27me3 deposition, H3K4me3 demethylation, H3K9, H3K14, H3K27, and H4K16 deacetylation, inhibition of RNA Polymerase II transcription elongation or Ser-5 dephosphorylation. The silencing fusion proteins also silenced many other genes with different efficacy, and a machine learning model could accurately predict the efficacy of each silencer based on various chromatin features of the target loci. These results provide a more comprehensive understanding of epigenetic regulatory pathways and provide an armament of tools for targeted manipulation of gene expression.
Hippocampal collagen as a potential target for post-surgical treatment; effects of whole-body vibration and exercise
Authors: Keijzer Noa , Oberman Klaske , Oroszi Tamás , Nyakas Csaba , van der Zee Eddy A , Schoemaker Regien G
Published: November 2022

Peripheral surgery may evoke neuroinflammation, associated with neuronal damage and consequently mental health problems. However, anti-inflammatory treatment showed limited therapeutic efficacy. Preservation of neuron integrity during neuroinflammation, by targeting their protective collagen sheet, may provide an alternative strategy. Whole-body vibration (WBV) and exercise combine anti-inflammatory and collagen-increasing effects in the periphery. The present study aimed to explore the therapeutic efficacy of postoperative WBV and exercise on hippocampal neuroinflammation and collagen expression.

Three months old male Wistar rats underwent abdominal surgery. Starting from one day after surgery, rats were submitted to WBV (10 min, once or twice daily, 30 Hz), running exercise (30 min, daily), or pseudo WBV/exercise, for two weeks. Rats were sacrificed and brain tissue was collected and processed for (immuno)histochemistry. Hippocampal microglia activity, total collagen content, and expression of fibrous and non-fibrous collagen subtypes were analysed.

Surgery was associated with increased microglia activity in the CA1 area, which was only partly reversed by the interventions. Surgery specifically reduced total collagen expression in the CA1 area, which was restored by both WBV and exercise. Collagen I was absent in the hippocampal granular layers. The surgery-induced decrease in collagen III expression in the CA1 area was not affected by either WBV or exercise. However, surgery increased collagen III in the CA2 (ns), CA3 and DG. Exercise, and to a lower extent WBV, seemed to (partly) reverse this effect. Collagen IV expression was not altered by surgery, but increased by WBV. No significant effects were observed on collagen VI expression.

WBV as well as exercise restored the surgery-induced declined collagen expression, while partly reversing microglia activation in the CA1 area. Moreover, effects on collagen appeared to be subtype- and region-specific, with overall similar effects of WBV and exercise. Nevertheless, the neuroprotective potential of postoperatively altered brain collagen needs further investigation.
Pharmacological Modulation of Autophagy Prevents Mutant SOD1G93AInduced Neurotoxicity in Experimental Models of Amyotrophic Lateral Sclerosis (ALS)
Authors: Bi Yue , Yan Xin , Yacipi Nazmiye , Duan Weisong , Li Chunyan , Thompson Martin , Shan Zhiying , Bi Lanrong
Published: November 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting from the progressive loss of both upper and lower motor neurons in the cerebral cortex, brainstem, and spinal cord. Currently, there are only two drugs, Riluzole (Rilutek) and Edaravone (Radicava), approved by FDA for ALS treatment. These two drugs are very expensive with only a few months of life extension. So far, there is no cure for ALS. Aberrant protein aggregation in motor neurons is an intracellular hallmark of ALS. The disturbance in protein homeostasis may contribute to the onset and progression of ALS. Autophagy plays an important role in degrading misfolded proteins, thereby preventing their aggregation. Pharmacological manipulation of autophagy has been proposed as a new therapeutic approach for treating ALS. IADB, a novel indole alkaloid derivative, has been reported to exert mitochondrial protection and cardioprotection through its autophagy-modulating potential. Our present study attempted to examine whether IADB has therapeutic potential in SOD1G93A-associated experimental models of ALS. We found that IADB could promote the clearance of SOD1G93Aaggregates and reduce the overproduction of mitochondrial reactive oxygen species (mtROS) in motor neuron-like NSC-34 cells transfected with SOD1G93A. We further examined the IADB in a SOD1-G93A mouse model of ALS. Administration of IADB started at the age of 55 days until the end stage of the disease. IADB treatment significantly increased LC3-II levels and decreased human SOD1 levels and p62 expression in the spinal cords of SOD1G93Amice, suggesting that IADB treatment could induce autophagy activation and promote clearance of mutant SOD1 aggregates in this mouse model of ALS. Moreover, IADB treatment could alleviate the activation of microglia and astrocytes and reduce mitochondrial oxidative damage in the spinal cord of SOD1G93Amice. Finally, we demonstrated that IADB treatment could improve motor performance and delay the onset and progression of the disease in a mouse model of ALS. The neuroprotective effects of IADB may mainly originate from its autophagy-promoting property.
Modification of blood-based (IgG) to salivary-based (IgA) ELISA for Inflammatory Bowel Disease Diagnostic: Tumor necrosis factor (TNF) alpha quantification
Authors: Kim Doeun , Ganesh Anjana , Riedel Timothy E.
Published: November 2022

Approximately 1.6 million people in the United States are struggling with Inflammatory bowel disease. Even though there are a number of diagnostic tools present, including MRI, CT scan, and laboratory tests, the public still lacks access to diagnostic tools due to their expensive costs and needs for the labor of trained phlebotomists. In response, this study focused on modification from blood based enzyme-linked immunoassay (ELISA) to salivary based ELISA in order to expand its accessibility. A 1mL saliva sample was spiked with 1 ± 0.01 μg/mL lyophilized IgG TNFα proteins, and the unspiked saliva was used as a control to test the modified diagnostic. Saliva samples were processed through centrifugation and syringe filtration steps. The change in color between a serum and salivary ELISA kit using either centrifugation or syringe filtration steps was measured by a Color Analysis app that compared red, green and blue values and a microtiter plate reader. The new protocol of salivary-based ELISA lost sensitivity from 31.5pg/mL to 15.6pg/mL of TNFα protein concentration. The best centrifugation method was when a combination of stock saliva and buffer was used before spiking the sample. This means that we can modify the current serum based diagnostic tool to a salivary diagnostic using centrifugation to filter the sample and implement it in developing countries due to its lower cost.
SUMOylation regulates Lem2 function in centromere clustering and silencing
Authors: Strachan Joanna , Leidecker Orsolya , Spanos Christos , Coz Clementine Le , Chapman Elliott , Arsenijevic Ana , Zhang Haidao , Zhao Ning , Bayne Elizabeth H.
Published: November 2022

Regulation by the small modifier SUMO is heavily dependent on spatial control of enzymes that mediate the attachment and removal of SUMO on substrate proteins. Here we show that in fission yeast, delocalisation of the SUMO protease Ulp1 from the nuclear envelope results in centromeric defects that can be attributed to hyper-SUMOylation at the nuclear periphery. Unexpectedly, we find that while this localised hyper-SUMOylation impairs centromeric silencing, it can also enhance centromere clustering. Moreover, both effects are at least partially dependent on SUMOylation of the inner nuclear membrane protein Lem2. Lem2 has previously been implicated in diverse biological processes, including the promotion of both centromere clustering and silencing, but how these distinct activities are coordinated was unclear; our observations suggest a model whereby SUMOylation may serve as a regulatory switch, modulating Lem2 interactions with competing partner proteins to balance its roles in alternative pathways. Our findings also reveal a previously unappreciated role for SUMOylation in promoting centromere clustering.
The dissociative role of bursting and non-bursting neural activity in the oscillatory nature of functional brain networks
Authors: Cordier Alix , Mary Alison , Vander Ghinst Marc , Goldman Serge , De Tiège Xavier , Wens Vincent
Published: November 2022

The oscillatory nature of intrinsic brain networks is largely taken for granted in the systems neuroscience community. However, the hypothesis that brain rhythms—and by extension transient bursting oscillations—underlie functional networks has not been demonstratedper se. Electrophysiological measures of functional connectivity are indeed affected by the power bias, which may lead to artefactual observations of spectrally specific network couplings not genuinely driven by neural oscillations, bursting or not. We investigate this crucial question by introducing a unique combination of a rigorous mathematical analysis of the power bias in frequency-dependent amplitude connectivity with a neurobiologically informed model of cerebral background noise based on hidden Markov modeling of resting-state magnetoencephalography (MEG). We demonstrate that the power bias may be corrected by a suitable renormalization depending nonlinearly on the signal-to-noise ratio, with noise identified as non-bursting oscillations. Applying this correction preserves the spectral content of amplitude connectivity, definitely proving the importance of brain rhythms in intrinsic functional networks. Our demonstration highlights a dichotomy between spontaneous oscillatory bursts underlying network couplings and non-bursting oscillations acting as background noise but whose function remains unsettled.

Significance statement

Brain rhythms are paramount electrophysiological correlates of human cerebral activity as they coordinate neurons across distinct brain areas and establish neural synchronization. Spontaneous cortical oscillations, and particularly transient “bursts” of oscillations, also appear as the main electrophysiological subtrate of intrinsic functional brain networks. However, we argue that this oscillatory theory of brain networks, despite being widely accepted, should be requestioned due to a critical bias in electrophysiological measures of network connectivity. Here, we combined mathematical and neurobiological modeling techniques with magnetoencephalography recordings to set this theory on firm and rigorous grounds. Key to our analysis are scarcely studied non-bursting cortical oscillations. Although their precise function remains elusive, our results reveal that dissociating bursting and non-bursting oscillations is fundamental to the rigorous interpretation of electrophysiological network connectivity.
CineFinch: An animated female zebra finch for studying courtship interactions
Authors: Phaniraj Nikhil , Joshi Sanjana , Trimbake Pradeepkumar , Pujari Aditya , Ramadurai Samyuktha , Kalra Shikha , Ratnaparkhi Nikhil , Rajan Raghav
Published: November 2022

Dummies, videos and computer animations have been used extensively in animal behaviour to study simple social interactions. These methods allow complete control of one interacting animal, making it possible to test hypotheses about the significance and relevance of different elements of animal displays. Recent studies have demonstrated the potential of videos and interactive displays for studying more complex courtship interactions in the zebra finch, a well-studied songbird. Here, we extended these techniques by developing an animated female zebra finch and showed that ~40% of male zebra finches (n=5/12) sing to this animation. To study real-time social interactions, we developed two possible methods for closed loop control of animations; (1) an arduino based system to initiate videos/animations based on perch hops and (2) a video game engine based system to change animations. Overall, our results provide an important tool for understanding the dynamics of complex social interactions during courtship.

SUMMARY STATEMENT

We develop and test an animation of a female zebra finch to study song and courtship interactions in the male zebra finch.
Alterations in intestinal Proteobacteria and antimicrobial resistance gene burden in individuals administered microbial ecosystem therapeutic (MET-2) for recurrentClostridioides difficileinfection
Authors: Rooney Ashley M. , Cochrane Kyla , Fedsin Stephanie , Yao Samantha , Anwer Shaista , Dehmiwal Satyender , Hota Susy , Poutanen Susan , Allen-Vercoe Emma , Coburn Bryan ,   the MTOP Investigators
Published: November 2022

Intestinal colonisation with pathogens and antimicrobial resistant organisms (AROs) is associated with increased risk of infection. Fecal microbiota transplant (FMT) has successfully been used to cure recurrentClostridioides difficileinfection (rCDI) and to decolonise intestinal AROs. However, FMT has significant practical barriers to implementation. A microbial consortium, microbial ecosystem therapeutic (MET)-2, is an alternative to FMT for the treatment of rCDI. It is unknown whether MET-2 is associated with decreases in pathogens and antimicrobial resistance genes (ARGs). We conducted a post-hoc metagenomic analysis of stool collected from two interventional studies of MET-2 (published) and FMT (unpublished) for rCDI treatment to understand if MET-2 had similar effects to FMT for decreasing pathogens and ARGs as well as increasing anaerobes. Patients were included in the current study if baseline stool had Proteobacteria relative abundance ≥10% by metagenomic sequencing. We assessed pre- and post-treatment Proteobacteria, obligate anaerobe and butyrate-producer relative abundances and total ARGs. MET-2 and FMT were associated with decreases in Proteobacteria relative abundance as well as increases in obligate anaerobe and butyrate-producer relative abundances. The microbiota response remained stable over 4 or 6 months for MET-2 and FMT, respectively. MET-2, but not FMT, was associated with a decrease in the total number of ARGs. MET-2 is a potential therapeutic strategy for ARO/ARG decolonisation and anaerobe repletion.
Methyl-SNP-seq reveals dual readouts of methylome and variome at molecule resolution while enabling target enrichment
Authors: Yan Bo , Wang Duan , Vaisvila Romualdas , Sun Zhiyi , Ettwiller Laurence
Published: November 2022

Covalent modifications of genomic DNA are crucial for most organisms to survive. Amplicon-based high-throughput sequencing technologies erase all DNA modifications to retain only sequence information for the four canonical nucleobases, necessitating specialized technologies for ascertaining epigenetic information. To also capture base modification information, we developed Methyl-SNP-seq, a technology that takes advantage of the complementarity of the double helix to extract the methylation and original sequence information from a single DNA molecule. More specifically, Methyl-SNP-seq uses bisulfite conversion of one of the strands to identify cytosine methylation while retaining the original four-bases sequence information on the other strand. As both strands are locked together to link the dual readouts on a single paired-end read, Methyl-SNP-seq allows detecting the methylation status of any DNA even without a reference genome. Because one of the strands retains the original four nucleotide composition, Methyl-SNP-seq can also be used in conjunction with standard sequence-specific probes for targeted enrichment and amplification. We show the usefulness of this technology in a broad spectrum of applications ranging from allele-specific methylation analysis in humans to identification of methyltransferase specificity in complex bacterial communities.
Crystal structure of bis{3-(3,5-dichlorophenyl)-5-[6-(1H-pyrazol-1-yl)pyridin-2-yl]-4H-1,2,4-triazol-4-ido}iron(II) methanol disolvate
Authors: Znovjyak Kateryna , Seredyuk Maksym , Fritsky Igor O. , Sliva Tatiana Y. , Amirkhanov Vladimir M. , Malinkin Sergey O. , Shova Sergiu
Published: November 2022

The asymmetric unit of the title compound, [FeII(C16H9Cl2N6)2]·2CH3OH, consists of half of a charge-neutral complex molecule and a discrete methanol molecule. The planar anionic tridentate ligand 2-[5-(3,5-dichlorophenyl)-4H-1,2,4-triazol-3-ato]-6-(1H-pyrazol-1-yl)pyridine coordinates to the FeII ion through the N atoms of the pyrazole, pyridine and triazole groups, forming a coordination sphere of the central ion that deviates moderately from an octahedral geometry. The average Fe—N bond distance is 1.953 Å, indicating the low-spin state of the FeII ion. The cone-like-shaped molecules, nested into each other, are linked through double weak C—H(pz)...π(ph) interactions into mono-periodic columns, which are further linked through weak C—H...N′/C′ interactions into di-periodic layers. The layers interact through double weak C–H(ph)...Cl bonds with neighbouring molecules. Energy framework analysis at the B3LYP/6–31 G(d,p) theory level reproduces the strong interaction within the layers and the weaker interlayer interactions. Intermolecular contacts were quantified using Hirshfeld surface analysis and two-dimensional fingerprint plots, the relative contributions of the contacts to the crystal packing being H...H 26.1%, H...C/C...H 24.4%, H...Cl/Cl...H 18.9% and H...N/N...H 12.1%.