bluuebunny/crossref_metadata_2025 huggingface dataset:
A Regional Approach to Building Digital Archives Capacity in Uganda
Authors: Lowry James , Luyomba David
Published: April 2022

In Uganda, records and archives management in government ministries, departments and agencies (MDAs) is the responsibility of the Ministry of Public Service through the Records and Information Management Department (DRIM). The Uganda National Archives is a section of DRIM. Officially, the Department's responsibilities include:

initiating and developing records management and archives administration policies

planning and budgeting for records management and archives administration programmes

giving guidance in the management of current records, semi-current and non-current records

co-ordinating the implementation of records and achives laws and policies

developing guidelines and procedures for records and archives administration

sensitising records creators and members of the public to enhance awareness on the importance of records

designing career development plans for records and archives staff, ensuring that government organisations follow good records management practice managing public records in all media or formats, including digital records
Seroprevalence and dynamics of anti-SARS-CoV-2 antibody among healthcare workers following ChAdOx1 nCoV-19 vaccination
Authors: Sarkar Soma , Das Shantanab , Choudhury Kabita , Mukherjee Saibal , Chatterjee Raghunath
Published: April 2022

Health care workers (HCWs) are in a higher risk of acquiring the disease owing to their regular contact with the patients. The aim of this study is to evaluate the seroprevalence among HCWs pre- and post-vaccination. The serological assessment of anti-SARS-CoV-2 antibody was conducted in pre- and post-vaccination of first or both doses of the ChAdOx1 nCoV-19 vaccine and followed up to 8 months for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and antibody titre. The neutralising antibody was positively correlated with IgG and total antibody. IgG was significantly decreased after 4–6 months post-infection. Almost all HCWs developed IgG after 2 doses of vaccine with comparable IgG to that of the infected HCWs. A follow-up of 6 to 8 months post vaccination showed a significant drop in antibody titre, while 56% of them didn't show a detectable level of IgG, suggesting the need for a booster dose. Around 21% of the vaccinated HCWs with significantly low antibody titre were infected with the SARS-CoV-2, but a majority of them showed mild symptoms and recovered in home isolation without any O2 support. We noticed the effectiveness of the ChAdOx1 nCoV-19 vaccine as evident from the low rate of breakthrough infection with any severe symptoms.
Last Meal for the Monks. Human Ecology, Food Prescriptions and Manipulation from a Sealed Archaeological Context. Case Study of San Vincenzo al Volturno Abbey, Molise, Southern Italy, Late Ninth Centuryad
Authors: Carannante Alfredo , Chilardi Salvatore , Solinas Francesco
Published: April 2022

Human communities belonging to different times and places often adopt a set of ideal rules, sometimes related to alimentary prescriptions. For different reasons, foods and/or specific resources are, in fact, prohibited to some social or religious groups, but sometimes these can elaborate special strategies to find a compromise between a high social status and the access to ‘prohibited’ resources. For past societies, a careful archaeological study, crossing data emerging from a multidisciplinary approach, written contemporary sources and the rules the community must follow, can depict what was an interplay of ideal rules and actual practice. The paper aims to study a significant population of the past, namely an early medieval monastic community, from a human ecology perspective, but also investigating food storage and preparation at the time, along with the practical respect of the Benedictine Rule about foods with its social implications. The site under study is San Vincenzo Abbey, one of the most important monastic power centres in Italy, which was destroyed in 881adby a Saracen raid followed by a destructive fire. This caused the collapse of some structures sealing the contexts of the kitchen's complex, thereby preserving many bioarchaelogical remains related to daily monastic life.
The Dublin Convention and the Introduction of the ‘First Entry Rule’ in the Allocation of Asylum Seekers in Europe
Authors: Lott Gaia
Published: April 2022

The Dublin Convention (1990) was the first binding agreement on asylum between the member states of the European Community. It defined the criteria that determined responsibility for the examination of asylum applications lodged in their territories. Given the contemporary discussions about the system that derived from it, the paper reflects on one of its main criteria: the first entry principle. Drawing on archival research in Belgium, France and the United Kingdom, the essay shows how the inclusion of the first entry principle was far more than a matter of course. It was influenced by the Schengen process and the establishment of the single market, previous North-South tensions over migratory issues, and governments’ (in)capacity to predict future developments. The inclusion of the first entry principle contributed to assimilating asylum policy with migration control, creating the premises for the subsequent burden-sharing problems and readmission agreement practices.
Repeated extracorporeal membrane oxygenation for support of an Adult with Congenital Heart Disease and reperfusion pulmonary oedema
Authors: Stukov Yuriy , Jacobs Jeffery P. , Cornman Jessica , Cruz Beltran Susanna , Moguillansky Diego , Bleiweis Mark S. , Peek Giles J.
Published: April 2022

We present the case of 28-year-old woman with a history of complex congenital cardiac surgery who developed cardiovascular collapse with reperfusion pulmonary oedema and right ventricular failure after surgical replacement of a severely stenosed right ventricle to pulmonary artery conduit. She required two separate episodes of support with extracorporeal membrane oxygenation and is alive and well 6 months after her initial cardiorespiratory crisis. We believe that consideration of a second period of support with extracorporeal membrane oxygenation is appropriate for select adults with CHD, provided they have a potentially reversible cause of postoperative cardiorespiratory collapse.

Our case provides several important lessons: (1) adults with CHD with severe postcardiotomy cardiorespiratory failure may potentially be salvaged even if they require multiple runs of extracorporeal membrane oxygenation; (2) adults with CHD with severe postcardiotomy respiratory failure with adequate cardiac function may potentially be salvaged with veno-venous extracorporeal membrane oxygenation; and (3) patients supported with extracorporeal membrane oxygenation will benefit from care from a skilled multidisciplinary team who are able to focus on the support of the function of the organs of the patient whilst providing nutrition and mobilisation.
Prediction in challenging situations: Most bilinguals can predict upcoming semantically-related words in their L1 source language when interpreting
Authors: Liu Yiguang , Hintz Florian , Liang Junying , Huettig Falk
Published: April 2022

Prediction is an important part of language processing. An open question is to what extent people predict language in challenging circumstances. Here we tested the limits of prediction by asking bilingual Dutch native speakers to interpret Dutch sentences into their English counterparts. In two visual world experiments, we recorded participants’ eye movements to co-present visual objects while they engaged in interpreting tasks (consecutive and simultaneous interpreting). Most participants showed anticipatory eye movements to semantically-related upcoming target words in their L1 source language during both consecutive and simultaneous interpretation. A quarter of participants during simultaneous interpretation however did not move their eyes, an extremely unusual participant behaviour in visual world studies. Overall, the findings suggest that most people predict in the source language under challenging interpreting situations. Further work is required to understand the causes of the absence of (anticipatory) eye movements during simultaneous interpretation in a substantial subset of individuals.
Impact of the external school food environment on the associations of internal school food environment with high schoolers’ diet and BMI
Authors: Betts Grace M , Schwedhelm Carolina , Lipsky Leah M , Haynie Denise L , Nansel Tonja R
Published: April 2022

Objective:

To examine associations of school food availability with student intake frequency and BMI, and whether the number of neighbourhood food outlets modifies these associations.

Design:

Baseline assessment of a nationally representative cohort study of US 10th graders. Students reported intake frequency of fruits and vegetables (FV), snacks and soda. BMI was calculated from measured height and weight. Administrators of seventy-two high schools reported the frequency of school availability of FV, snacks and soda. The number of food outlets within 1 km and 5 km were linked with geocoded school addresses. Data were analysed using adjusted linear and logistic mixed models with multiple imputation for missing data.

Setting:

US 2009–2010.

Participants:

Totally, 2263 US 10th graders from the Next Generation Health Study (NEXT).

Results:

Greater school FV availability was positively associated with student FV intake. Food outlets within 5 km of schools (but not 1 km) attenuated the association of school FV availability with student intake; this was no longer significant at schools with > 58 food outlets within 5 km. School food availability was not associated with student BMI or student snack or soda intake.

Conclusions:

School food availability was associated with student intake of FV, but not with snacks, soda or BMI. Attenuation of the observed associations by the school neighbourhood food environment indicates a need to find ways to support healthy student eating behaviours in neighbourhoods with higher food outlet density.
Harnessing the potential of artificial intelligence for humanitarian action: Opportunities and risks
Authors: Beduschi Ana
Published: April 2022

Data-driven artificial intelligence (AI) technologies are progressively transforming the humanitarian field, but these technologies bring about significant risks for the protection of vulnerable individuals and populations in situations of conflict and crisis. This article investigates the opportunities and risks of using AI in humanitarian action. It examines whether and under what circumstances AI can be safely deployed to support the work of humanitarian actors in the field. The article argues that AI has the potential to support humanitarian actors as they implement a paradigm shift from reactive to anticipatory approaches to humanitarian action. However, it recommends that the existing risks, including those relating to algorithmic bias and data privacy concerns, must be addressed as a priority if AI is to be put at the service of humanitarian action and not to be deployed at the expense of humanitarianism. In doing so, the article contributes to the current debates on whether it is possible to harness the potential of AI for responsible use in humanitarian action.
Humanitäre Hilfe
Authors: Gardemann Joachim
Published: April 2022

Joachim Gardemann schildert Begegnungen und Erfahrungen eines Facharztes für Humanitäre Hilfe des DRKs, die er weltweit in Krisengebieten gesammelt hat. Er beschreibt Menschen in existenziellen Notsituationen, die an der Grenze zu Ruanda einen Genozid traumatisiert überlebt haben. Menschen, die vor Bürgerkriegen im Kongo geflohen oder dem Kosovokrieg entronnen sind. Er zeichnet das Leid von Menschen im Iran, in China und Haiti nach, denen schwere Erdbeben Angehörige und alle Habseligkeiten genommen haben. Menschen, die den Wirren der Bürgerkriege im Sudan und in Syrien entflohen sind, begegnet er in Momenten größter Zerbrechlichkeit und im Schutz und Schmutz eines Flüchtlingslagers in Jordanien. In anrührenden Porträts skizziert er Opfer der Tsunamikatastrophe in Sri Lanka. Die Verheerungen, die die Ebola-Epidemie in Sierra Leone angerichtet hat, schildert er eindrücklich. Denen, die an Ebola gestorben sind, die im Kampf gegen Ebola als Ärzte und Pflegende ihr Leben gelassen haben und den Davongekommenen setzt er ein würdiges Denkmal. Er liefert eine weise Antwort auf die Frage «Warum helfen?» in humanitären Krisensituationen notwendig und ein Gebot der Mitmenschlichkeit ist. Seine Aquarelle und Porträts von Menschen nehmen sich Zeit für sie, würdigen ihr schweres Leiden und trotzen allen Verwüstungen mit einer Poesie des Tuns.
Seawater Cadmium in the Florida Straits Over the Holocene and Implications for Upper AMOC Variability
Authors: Valley Shannon G. , Lynch‐Stieglitz Jean , Marchitto Thomas M. , Oppo Delia W.
Published: April 2022

Atlantic Meridional Overturning Circulation (AMOC) plays a central role in the global redistribution of heat and precipitation during both abrupt and longer‐term climate shifts. Over the next century, AMOC is projected to weaken due to greenhouse gas warming, though projecting its future behavior is dependent on a better understanding of how AMOC changes are forced. Seeking to resolve an apparent contradiction of AMOC trends from paleorecords of the more recent past, we reconstruct seawater cadmium, a nutrient‐like tracer, in the Florida Straits over the last ∼8,000 years, with emphasis on the last millennium. The gradual reduction in seawater Cd over the last 8,000 years could be due to a reduction in AMOC, consistent with cooling Northern Hemisphere temperatures and a southward shift of the Intertropical Convergence Zone. However, it is difficult to reconcile this finding with evidence for an increase in geostrophic flow through the Florida Straits over the same time period. We combine data from intermediate water depth sediment cores to extend this record into the Common Era at sufficient resolution to address the broad scale changes of this time period. There is a small decline in the Cd concentration in the Late Little Ice Age relative to the Medieval Climate Anomaly, but this change was much smaller than the changes observed over the Holocene and on the deglaciation. This suggests that any trend in the strength of AMOC over the last millennium must have been very subtle.
Thank You to Our 2021 Reviewers
Authors: Faccenna Claudio , Asimow Paul , Behr Whitney , Blichert‐Toft Janne , Edmonds Marie , Feinberg Joshua , Lithgow‐Bertelloni Carolina R. , Long Maureen , Paytan Adina , van der Beek Peter , Williams Branwen
Published: April 2022

Key Point

The editors thank the 2021 peer reviewers
Subthalamic nucleus stabilizes movements by reducing neural spike variability in monkey basal ganglia
Authors: Hasegawa Taku , Chiken Satomi , Kobayashi Kenta , Nambu Atsushi
Published: April 2022

The subthalamic nucleus projects to the external and internal pallidum, the modulatory and output nuclei of the basal ganglia, respectively, and plays an indispensable role in controlling voluntary movements. However, the precise mechanism by which the subthalamic nucleus controls pallidal activity and movements remains elusive. Here, we utilize chemogenetics to reversibly reduce neural activity of the motor subregion of the subthalamic nucleus in three macaque monkeys (Macaca fuscata, both sexes) during a reaching task. Systemic administration of chemogenetic ligands prolongs movement time and increases spike train variability in the pallidum, but only slightly affects firing rate modulations. Across-trial analyses reveal that the irregular discharges in the pallidum coincides with prolonged movement time. Reduction of subthalamic activity also induces excessive abnormal movements in the contralateral forelimb, which are preceded by subthalamic and pallidal phasic activity changes. Our results suggest that the subthalamic nucleus stabilizes pallidal spike trains and achieves stable movements.
A fungal extracellular effector inactivates plant polygalacturonase-inhibiting protein
Authors: Wei Wei , Xu Liangsheng , Peng Hao , Zhu Wenjun , Tanaka Kiwamu , Cheng Jiasen , Sanguinet Karen A. , Vandemark George , Chen Weidong
Published: April 2022

Plant pathogens degrade cell wall through secreted polygalacturonases (PGs) during infection. Plants counteract the PGs by producing PG-inhibiting proteins (PGIPs) for protection, reversibly binding fungal PGs, and mitigating their hydrolytic activities. To date, how fungal pathogens specifically overcome PGIP inhibition is unknown. Here, we report an effector, Sclerotinia sclerotiorum PGIP-INactivating Effector 1 (SsPINE1), which directly interacts with and functionally inactivates PGIP. S. sclerotiorum is a necrotrophic fungus that causes stem rot diseases on more than 600 plant species with tissue maceration being the most prominent symptom. SsPINE1 enhances S. sclerotiorum necrotrophic virulence by specifically interacting with host PGIPs to negate their polygalacturonase-inhibiting function via enhanced dissociation of PGIPs from PGs. Targeted deletion of SsPINE1 reduces the fungal virulence. Ectopic expression of SsPINE1 in plant reduces its resistance against S. sclerotiorum. Functional and genomic analyses reveal a conserved virulence mechanism of cognate PINE1 proteins in broad host range necrotrophic fungal pathogens.
Unveiling the charge transfer dynamics steered by built-in electric fields in BiOBr photocatalysts
Authors: Luo Zhishan , Ye Xiaoyuan , Zhang Shijia , Xue Sikang , Yang Can , Hou Yidong , Xing Wandong , Yu Rong , Sun Jie , Yu Zhiyang , Wang Xinchen
Published: April 2022

Construction of internal electric fields (IEFs) is crucial to realize efficient charge separation for charge-induced redox reactions, such as water splitting and CO2 reduction. However, a quantitative understanding of the charge transfer dynamics modulated by IEFs remains elusive. Here, electron microscopy study unveils that the non-equilibrium photo-excited electrons are collectively steered by two contiguous IEFs within binary (001)/(200) facet junctions of BiOBr platelets, and they exhibit characteristic Gaussian distribution profiles on reduction facets by using metal co-catalysts as probes. An analytical model justifies the Gaussian curve and allows us to measure the diffusion length and drift distance of electrons. The charge separation efficiency, as well as photocatalytic performances, are maximized when the platelet size is about twice the drift distance, either by tailoring particle dimensions or tuning IEF-dependent drift distances. The work offers great flexibility for precisely constructing high-performance particulate photocatalysts by understanding charge transfer dynamics.
Rich nature of Van Hove singularities in Kagome superconductor CsV3Sb5
Authors: Hu Yong , Wu Xianxin , Ortiz Brenden R. , Ju Sailong , Han Xinloong , Ma Junzhang , Plumb Nicholas C. , Radovic Milan , Thomale Ronny , Wilson Stephen D. , Schnyder Andreas P. , Shi Ming
Published: April 2022

The recently discovered layered kagome metals AV3Sb5 (A = K, Rb, Cs) exhibit diverse correlated phenomena, which are intertwined with a topological electronic structure with multiple van Hove singularities (VHSs) in the vicinity of the Fermi level. As the VHSs with their large density of states enhance correlation effects, it is of crucial importance to determine their nature and properties. Here, we combine polarization-dependent angle-resolved photoemission spectroscopy with density functional theory to directly reveal the sublattice properties of 3d-orbital VHSs in CsV3Sb5. Four VHSs are identified around the M point and three of them are close to the Fermi level, with two having sublattice-pure and one sublattice-mixed nature. Remarkably, the VHS just below the Fermi level displays an extremely flat dispersion along MK, establishing the experimental discovery of higher-order VHS. The characteristic intensity modulation of Dirac cones around K further demonstrates the sublattice interference embedded in the kagome Fermiology. The crucial insights into the electronic structure, revealed by our work, provide a solid starting point for the understanding of the intriguing correlation phenomena in the kagome metals AV3Sb5.
Cell-lineage controlled epigenetic regulation in glioblastoma stem cells determines functionally distinct subgroups and predicts patient survival
Authors: Lu Xi , Maturi Naga Prathyusha , Jarvius Malin , Yildirim Irem , Dang Yonglong , Zhao Linxuan , Xie Yuan , Tan E-Jean , Xing Pengwei , Larsson Rolf , Fryknäs Mårten , Uhrbom Lene , Chen Xingqi
Published: April 2022

There is ample support for developmental regulation of glioblastoma stem cells. To examine how cell lineage controls glioblastoma stem cell function, we present a cross-species epigenome analysis of mouse and human glioblastoma stem cells. We analyze and compare the chromatin-accessibility landscape of nine mouse glioblastoma stem cell cultures of three defined origins and 60 patient-derived glioblastoma stem cell cultures by assay for transposase-accessible chromatin using sequencing. This separates the mouse cultures according to cell of origin and identifies three human glioblastoma stem cell clusters that show overlapping characteristics with each of the mouse groups, and a distribution along an axis of proneural to mesenchymal phenotypes. The epigenetic-based human glioblastoma stem cell clusters display distinct functional properties and can separate patient survival. Cross-species analyses reveals conserved epigenetic regulation of mouse and human glioblastoma stem cells. We conclude that epigenetic control of glioblastoma stem cells primarily is dictated by developmental origin which impacts clinically relevant glioblastoma stem cell properties and patient survival.
Natural variability has dominated Atlantic Meridional Overturning Circulation since 1900
Authors: Latif Mojib , Sun Jing , Visbeck Martin , Hadi Bordbar M.
Published: April 2022

There is debate about slowing of the Atlantic Meridional Overturning Circulation (AMOC), a key component of the global climate system. Some focus is on the sea surface temperature (SST) slightly cooling in parts of the subpolar North Atlantic despite widespread ocean warming. Atlantic SST is influenced by the AMOC, especially on decadal timescales and beyond. The local cooling could thus reflect AMOC slowing and diminishing heat transport, consistent with climate model responses to rising atmospheric greenhouse gas concentrations. Here we show from Atlantic SST the prevalence of natural AMOC variability since 1900. This is consistent with historical climate model simulations for 1900–2014 predicting on average AMOC slowing of about 1 Sv at 30° N after 1980, which is within the range of internal multidecadal variability derived from the models’ preindustrial control runs. These results highlight the importance of systematic and sustained in-situ monitoring systems that can detect and attribute with high confidence an anthropogenic AMOC signal.
A new cynodont from the Upper Triassic Los Colorados Formation (Argentina, South America) reveals a novel paleobiogeographic context for mammalian ancestors
Authors: Gaetano L. C. , Abdala F. , Seoane F. D. , Tartaglione A. , Schulz M. , Otero A. , Leardi J. M. , Apaldetti C. , Krapovickas V. , Steimbach E.
Published: April 2022

Probainognathia is a derived lineage of cynodonts which encompass Mammalia as their crown-group. The rich record of probainognathians from the Carnian of Argentina contrasts with their Norian representation, with only one named species. Here we describe a new probainognathian, Tessellatia bonapartei gen. et sp. nov., from the Norian Los Colorados Formation of the Ischigualasto-Villa Unión Basin of Argentina. The new taxon, represented by a partial cranium with associated lower jaws, was analyzed through neutron and X-rays micro-tomography (μCT). The high-resolution neutron μCT data allowed the identification of a unique character combination, including features inaccessible through traditional techniques. We constructed the largest phylogenetic data matrix of non-mammalian cynodonts. The new species and its sister taxon, the Brazilian Therioherpeton cargnini, are recovered as probainognathians, closely related to Mammaliamorpha. We conducted the first quantitative paleobiogeographic analysis of non-mammalian cynodonts, focusing in probainognathians. The results indicate that Probainognathia and Mammaliamorpha originated in southwestern Gondwana (in the Brazilian Paraná Basin), which was an important center of diversification during the Triassic. Finally, the Chinese Lufeng Basin is identified as the ancestral area of Mammaliaformes. These new findings, besides adding to the knowledge of the poorly represented Norian cynodonts from the Los Colorados Formation, are significant to improve our understanding of probainognathian diversity, evolution, and paleobiogeographic history.
Evaluation and application of the CROPGRO-soybean model for determining optimum sowing windows of soybean in the Nigeria savannas
Authors: Bebeley J. F. , Kamara A. Y. , Jibrin J. M. , Akinseye F. M. , Tofa A. I. , Adam A. M. , Kamai N. , Solomon R.
Published: April 2022

Soybean production is limited by poor soil fertility and unstable rainfall due to climate variability in the Nigeria savannas. There is a decline in the amount and duration of rainfall as one moves from the south to north of the savanna zones. The use of adapted soybean varieties and optimum sowing windows are avenues to increase productivity in the face of climate variability. Crop simulation models can be used as tools for the evaluation of alternative management options for a particular location, including fertilizer application rates, plant density, sowing dates and land use. In this study, we evaluated the performance of the Cropping System Model (CSM)-CROPGRO-Soybean to determine optimum sowing windows for three contrasting soybean varieties (TGX1835-10E, TGX1904-6F and TGX1951-3F) cultivated in the Nigeria savannas. The model was calibrated using data from ten field experiments conducted under optimal conditions at two sites (BUK and Dambatta) in Kano in the Sudan savanna (SS) agro-ecology over four growing seasons. Data for model evaluation were obtained from independent experiment for phosphorus (P) response trials conducted under rainfed conditions in two locations (Zaria and Doguwa) in the northern Guinea savanna (NGS) zone. The model calibration and evaluation results indicated good agreement between the simulated and observed values for the measured parameters. This suggests that the CROPGRO-Soybean model was able to accurately predict the performance of soybean in the Nigeria savannas. Results from long-term seasonal analysis showed significant differences among the agro-ecologies, sowing windows and the soybean varieties for grain yield. Higher yields are simulated among the soybean varieties in Zaria in the NGS than in Kano the SS and Jagiri in the southern Guinea savanna (SGS) agro-ecological zones. Sowing from June 1 to July 5 produced optimal yield of TGX1951-3F and TGX1835-10E beyond which yield declined in Kano. In Zaria and Jagiri the simulated results show that, sowing from June 1 to July 12 are appropriate for all the varieties. The variety TGX1951-3F performed better than TGX1904-6F and TGX1835-10E in all the agro-ecologies. The TGX1951-3F is, therefore, recommended for optimum grain yield in the savannas of northern Nigeria. However, the late maturing variety TGX1904-6F is not recommended for the SS due to the short growing season in this zone.
A novel ND1 mitochondrial DNA mutation is maternally inherited in growth hormone transgenesis in amago salmon (Oncorhynchus masou ishikawae)
Authors: Sato Tomohiko , Goto-Inoue Naoko , Kimishima Masaya , Toyoharu Jike , Minei Ryuhei , Ogura Atsushi , Nagoya Hiroyuki , Mori Tsukasa
Published: April 2022

Growth hormone (GH) transgenesis can be used to manipulate the growth performance of fish and mammals. In this study, homozygous and hemizygous GH-transgenic amago salmon (Oncorhynchus masou ishikawae) derived from a single female exhibited hypoglycemia. Proteomic and signal network analyses using iTRAQ indicated a decreased NAD+/NADH ratio in transgenic fish, indicative of reduced mitochondrial ND1 function and ROS levels. Mitochondrial DNA sequencing revealed that approximately 28% of the deletion mutations in the GH homozygous- and hemizygous-female-derived mitochondrial DNA occurred in ND1. These fish also displayed decreased ROS levels. Our results indicate that GH transgenesis in amago salmon may induce specific deletion mutations that are maternally inherited over generations and alter energy production.
The effects of short-term and long-term air pollution exposure on meibomian gland dysfunction
Authors: Hao Ran , Wan Yu , Zhao Liming , Liu Yang , Sun Min , Dong Jing , Xu Yanhui , Wu Feng , Wei Jinwen , Xin Xiangyang , Luo Zhongping , Lv Shuxuan , Li Xuemin
Published: April 2022

We aim to assess the effects of different air pollutants on meibomian gland dysfunction (MGD). As a prospective multicenter study, 864 patients were recruited from four different regions (i.e., coal, oil, steel, and living). The oil region had a significantly lower temperature and higher O3 and SO2 concentrations than other regions. Notably, participants in oil region presented with more frequent and serious MGD signs and higher cytokine levels (median interleukin 6 [IL-6] in oil: 2.66, steel: 0.96, coal: 0.38, living: 0.56; IL-8 in oil: 117.52, steel: 46.94, coal: 26.89, living: 33; vascular endothelial growth factor [VEGF] in oil: 25.09, steel: 14.02, coal: 14.02, living: 28.47). The short-term fluctuations of cytokine levels were associated with the changes in gas levels (PM2.5 and IL-8: β = 0.016 [0.004–0.029]; O3 and IL-6: β = 0.576 [0.386–0.702]; O3 and IL-8: β = 0.479 [0.369–0.890]; SO2 and VEGF: β = 0.021 [0.001–0.047]). After long-term exposure, lid margin neovascularization (r = 0.402), meibomian gland (MG) expression (r = 0.377), MG secretion (r = 0.303), MG loss (r = 0.404), and tear meniscus height (r = − 0.345) were moderately correlated with air quality index (AQI). Individuals in oil region had more serious MGD signs and higher cytokine levels. MGD is susceptible to long-term exposure to high AQI.
Mixture-modeling approach reveals global and local processes in visual crowding
Authors: Jimenez Mikel , Kimchi Ruth , Yashar Amit
Published: April 2022

Crowding refers to the inability to recognize objects in clutter, setting a fundamental limit on various perceptual tasks such as reading and facial recognition. While prevailing models suggest that crowding is a unitary phenomenon occurring at an early level of processing, recent studies have shown that crowding might also occur at higher levels of representation. Here we investigated whether local and global crowding interference co-occurs within the same display. To do so, we tested the distinctive contribution of local flanker features and global configurations of the flankers on the pattern of crowding errors. Observers (n = 27) estimated the orientation of a target when presented alone or surrounded by flankers. Flankers were grouped into a global configuration, forming an illusory rectangle when aligned or a rectangular configuration when misaligned. We analyzed the error distributions by fitting probabilistic mixture models. Results showed that participants often misreported the orientation of a flanker instead of that of the target. Interestingly, in some trials the orientation of the global configuration was misreported. These results suggest that crowding occurs simultaneously across multiple levels of visual processing and crucially depends on the spatial configuration of the stimulus. Our results pose a challenge to models of crowding with an early single pooling stage and might be better explained by models which incorporate the possibility of multilevel crowding and account for complex target-flanker interactions.
Time-series biological responses toward decellularized bovine tendon graft and autograft for 52 consecutive weeks after rat anterior cruciate ligament reconstruction
Authors: Itoh Masafumi , Imasu Hiroki , Takano Kazuya , Umezu Mitsuo , Okazaki Ken , Iwasaki Kiyotaka
Published: April 2022

There is an essential demand for developing biocompatible grafts for knee anterior cruciate ligament reconstruction (ACLR). This study investigated cell infiltration into decellularized bovine tendon xenografts using a rat knee ACLR model. Twelve-week-old Sprague–Dawley rats were used. At weeks 1, 2, 4, 8, 16, 26, and 52 (each period, n = 6) after ACLR, rats receiving decellularized bovine tendon (group D, n = 42) or autologous tendon (group A, n = 42) as grafts underwent peritibial bone tunnel bone mineral density (BMD), histological, and immunohistological assessments. BMD increased over time in both the groups until week 16 and then remained unchanged without exhibiting significant differences between the groups. Initially, cellularity in group D was lower than that in group A; however, by weeks 4–8, both the groups were comparable to the native anterior cruciate ligament group and cellularity remained unchanged until week 52. Initially, group A had more M1 macrophages, indicating inflammation, whereas group D had more M2 macrophages, indicating tissue regeneration. Nonetheless, the M1 and M2 macrophage counts of both the groups were comparable at most times. This study revealed the excellent recellularization and tendon–bone integration abilities of decellularized tendons using a cross-species model.
Molecular mechanisms of bifunctional vitamin D receptor agonist-histone deacetylase inhibitor hybrid molecules in triple-negative breast cancer
Authors: Barbier Camille , Mansour Ali , Ismailova Aiten , Sarmadi Fatemeh , Scarlata David A. , Bouttier Manuella , Zeitouni Camille , Wang Catherine , Gleason James L. , White John H.
Published: April 2022

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), and its analogues signal through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor, and have been extensively investigated as anticancer agents. 1,25D and its analogs have potential in combination therapies because they exhibit synergistic activities with other anticancer agents such as histone deacetylase inhibitors (HDACi). We have developed a series of hybrid molecules that combine HDACi within the backbone of a VDR agonist and thus represent fully integrated bifunctional molecules. They exhibit anti-tumor efficacy in reducing tumor growth and metastases in an aggressive model of triple-negative breast cancer. However, their solubility is limited by their hydrophobic diarylpentane cores. Our goals here were two-fold: (1) to improve the solubility of hybrids by introducing nitrogen into diarylpentane cores, and (2) to investigate the molecular mechanisms underlying their anti-tumor efficacy by performing comparative gene expression profiling studies with 1,25D and the potent HDACi suberoylanilide hydroxamic acid (SAHA). We found that substituting aryl with pyrydyl rings did not sacrifice bifunctionality and modestly improved solubility. Notably, one compound, AM-193, displayed enhanced potency as a VDR agonist and in cellular assays of cytotoxicity. RNAseq studies in triple negative breast cancer cells revealed that gene expression profiles of hybrids were very similar to that of 1,25D, as was that observed with 1,25D and SAHA combined. The effects of SAHA alone on gene expression were limited and distinct from those 1,25D or hybrids. The combined results suggest that efficacy of hybrids arises from targeting HDACs that do not have a direct role in gene regulation. Moreover, pathways analysis revealed that hybrids regulate numerous genes controlling immune cell infiltration into tumors and suppress the expression of several secreted molecules that promote breast cancer growth and metastasis.
No significant difference in intermediate key outcomes in men with low- and intermediate-risk prostate cancer managed by active surveillance
Authors: Cyll Karolina , Löffeler Sven , Carlsen Birgitte , Skogstad Karin , Plathan May Lisbeth , Landquist Martin , Haug Erik Skaaheim
Published: April 2022

Active surveillance (AS) is standard of care for patients with low-risk prostate cancer (PCa), but its feasibility in intermediate-risk patients is controversial. We compared outcomes of low- and intermediate-risk patients managed with multiparametric magnetic resonance imaging (mpMRI)-supported AS in a community hospital. Of the 433 patients enrolled in AS between 2009 and 2016, 358 complied with AS inclusion criteria (Cancer of the Prostate Risk Assessment (CAPRA) score ≤ 5, Gleason grade group (GGG) ≤ 2, clinical stage ≤ cT2 and prostate-specific antigen (PSA) ≤ 20 ng/ml) and discontinuation criteria (histological-, PSA-, clinical- or radiological disease reclassification). Of the 358 patients, 177 (49%) were low-risk and 181 (51%) were intermediate-risk. Median follow-up was 4.2 years. The estimated 5-year treatment-free survival (TFS) was 56% (95% confidence interval [CI] 51–62%). Intermediate-risk patients had significantly shorter TFS compared with low-risk patients (hazard ratio 2.01, 95% CI 1.47–2.76, p < 0.001). There were no statistically significant differences in the rate of adverse pathology, biochemical recurrence-free survival and overall survival between low- and intermediate-risk patients. Two patients developed metastatic disease and three died of PCa. These results suggest that selected patients with intermediate-risk PCa may be safely managed by mpMRI-supported AS, but longer follow-up is necessary.
Transglutaminase 3 negatively regulates immune responses on the heart of the mosquito, Anopheles gambiae
Authors: Yan Yan , Ramakrishnan Abinaya , Estévez-Lao Tania Y. , Hillyer Julián F.
Published: April 2022

The immune and circulatory systems of insects are functionally integrated. Following infection, immune cells called hemocytes aggregate around the ostia (valves) of the heart. An earlier RNA sequencing project in the African malaria mosquito, Anopheles gambiae, revealed that the heart-associated hemocytes, called periostial hemocytes, express transglutaminases more highly than hemocytes elsewhere in the body. Here, we further queried the expression of these transglutaminase genes and examined whether they play a role in heart-associated immune responses. We found that, in the whole body, injury upregulates the expression of TGase2, whereas infection upregulates TGase1, TGase2 and TGase3. RNAi-based knockdown of TGase1 and TGase2 did not alter periostial hemocyte aggregation, but knockdown of TGase3 increased the number of periostial hemocytes during the early stages of infection and the sequestration of melanin by periostial hemocytes during the later stages of infection. In uninfected mosquitoes, knockdown of TGase3 also slightly reduced the number of sessile hemocytes outside of the periostial regions. Taken altogether, these data show that TGase3 negatively regulates periostial hemocyte aggregation, and we hypothesize that this occurs by negatively regulating the immune deficiency pathway and by altering hemocyte adhesion. In conclusion, TGase3 is involved in the functional integration between the immune and circulatory systems of mosquitoes.
Five nanometer size highly positive silver nanoparticles are bactericidal targeting cell wall and adherent fimbriae expression
Authors: Pokhrel Lok R. , Jacobs Zachary L. , Dikin Dmitriy , Akula Shaw M.
Published: April 2022

To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH2–AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate–AgNPs) were nontoxic; and Ag+ ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate–AgNPs (0.5–10 µg/mL), whereas NH2–AgNPs (0.5–10 µg/mL) or Ag+ ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH2–AgNPs treatments, suggesting NH2–AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH2–AgNPs and the lack of toxicity of Citrate–AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.
Using virtual global landmark to improve incidental spatial learning
Authors: Liu Jia , Singh Avinash Kumar , Lin Chin-Teng
Published: April 2022

To reduce the decline of spatial cognitive skills caused by the increasing use of automated GPS navigation, the virtual global landmark (VGL) system is proposed to help people naturally improve their sense of direction. Designed to accompany a heads-up navigation system, VGL system constantly displays silhouette of global landmarks in the navigator’s vision as a notable frame of reference. This study exams how VGL system impacts incidental spatial learning, i.e., subconscious spatial knowledge acquisition. We asked 55 participants to explore a virtual environment and then draw a map of what they had explored while capturing electroencephalogram (EEG) signals and eye activity. The results suggest that, with the VGL system, participants paid more attention during exploration and performed significantly better at the map drawing task—a result that indicates substantially improved incidental spatial learning. This finding might kickstart a redesigning navigation aids, to teach users to learn a route rather than simply showing them the way.
Short and long-term costs of inbreeding in the lifelong-partnership in a termite
Authors: Eyer Pierre-André , Vargo Edward L.
Published: April 2022

Social life and lifelong partner commitments are expected to favor thorough partner choice, as an ill-suited partnership may have long-term consequences, adversely affecting the parents and spanning several cohorts of offspring. Here, we used ~1400 termite incipient colonies to estimate the short- and long-term costs of inbreeding upon the survival of the parents over a 15-month period, their productivity, and the resistance of their offspring toward pathogen pressure. We observed that foundation success was not influenced by the relatedness of partners, but by their levels of microbial load. We showed faster growth in inbred colonies with low levels of microbial load, revealing a potential tradeoff between pathogen defense and offspring production. Yet, inbreeding takes its toll later in colony development when offspring from incipient colonies face pathogen pressure. Although the success of a lifetime partnership is initially determined by the partner’s health, the cost of inbreeding in incipient colonies favors outbred colonies reaching maturity.
Hidden Markov modeling for maximum probability neuron reconstruction
Authors: Athey Thomas L. , Tward Daniel J. , Mueller Ulrich , Vogelstein Joshua T. , Miller Michael I.
Published: April 2022

Recent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron fluorescence. ViterBrain utilizes dynamic programming to compute the global maximizer of what we call the most probable neuron path. We applied our algorithm to imperfect image segmentations, and showed that it can follow axons in the presence of noise or nearby neurons. We also provide an interactive framework where users can trace neurons by fixing start and endpoints. ViterBrain is available in our open-source Python package .
Acceleration of enzymatic catalysis by active hydrodynamic fluctuations
Authors: Tripathi Ashwani Kr. , Das Tamoghna , Paneru Govind , Pak Hyuk Kyu , Tlusty Tsvi
Published: April 2022

The cellular milieu is teeming with biochemical nano-machines whose activity is a strong source of correlated non-thermal fluctuations termed active noise. Essential elements of this circuitry are enzymes, catalysts that speed up the rate of metabolic reactions by orders of magnitude, thereby making life possible. Here, we examine the possibility that active noise in the cell, or in vitro, affects enzymatic catalytic rate by accelerating or decelerating the crossing rate of energy barriers during the reaction. Considering hydrodynamic perturbations induced by biochemical activity as a source of active noise, we evaluate their impact on the enzymatic cycle using a combination of analytic and numerical methods. Our estimates show that the fast component of the active noise spectrum  may significantly enhance the turnover rate of enzymes, while reactions remain practically unaffected by the slow noise spectrum. Revisiting the physics of barrier crossing under the influence of active hydrodynamic fluctuations suggests that the biochemical activity of macromolecules such as enzymes is coupled to active noise. Thus, we propose that enzymatic catalysis is a collective, many-body process in which enzymes may affect each other’s activity via long-range hydrodynamic interaction, with potential impact on biochemical networks in living and artificial systems alike.
Supramolecular Aspects of Magnetic Resonance Imaging
Authors: Tear Louise R. , Faulkner Stephen , M. Ó Máille Gearóid
Published: April 2022

Magnetic resonance imaging (MRI) contrast agents rely on supramolecular interactions for their function, since they rely on solvent exchange at a coordination complex. This chapter explores the ideas that underpin MRI, and goes on to discuss the importance of complex stability and the challenges inherent to responsive complexes that can detect changes in biology.
Molecular Imaging in Diagnosis and Treatment of Brain Tumours
Authors: Farrer Nicola J. , Evans Rhiannon J. , Morse Sophie V. , Long Nicholas J.
Published: April 2022

We provide an overview of the current status of brain tumours, their incidence and possible risk factors. The current treatment options, including surgery, immunotherapy, chemotherapy, radiotherapies and particle therapy are discussed, with a focus on how this can be informed by imaging techniques. Delivery of agents to the central nervous system is a key consideration; various strategies for penetrating (chemical modification, ultrasound) and circumventing (convection enhanced delivery) the blood–brain barriers are discussed. The most commonly used techniques for diagnosis of brain tumours (biopsy, magnetic resonance imaging, positron emission tomography) are described, along with less well-established techniques such as optical imaging, optical coherence tomography, photoacoustic imaging, ultrasound, X-ray computed tomography (CT), single photon emission computed tomography (SPECT) and Raman spectroscopy. We consider the aspects which can be highlighted by different methods, including an appraisal of their strengths and limitations, with discussion on the potential for targeting, and what information can be gained by imaging for both diagnosis and disease progression. The future potential for imaging in the diagnosis and treatment of brain tumours is then considered, with a focus on which properties are desirable for novel imaging agents.