bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic structure of the low-lying negative-parity states in the proton-neutron symplectic model
Authors: Ganev H. G.
Published: June 2020

The proton-neutron symplectic shell-model approach is applied to the description of the microscopic structure of the low-lying negative-parity states of the

K
π

=

0
1
−

and

K
π

=

1
1
−

bands in 154Sm and 238U without the introduction of additional degrees of freedom that are inherent to other approaches to odd-parity nuclear states. A good description of the energy levels of the two bands under consideration, as well as the reproduction of some energy splitting quantities which are usually introduced in the literature as a measure of the octupole correlations, is obtained for these two nuclei. Additionally, the low-energy B(E1) transition strengths between the states of the ground band and

K
π

=

0
1
−

band for the two nuclei are calculated in the extended proton-neutron symplectic model and compared with experiment. The results obtained reproduce well the experimental data for the two nuclei under consideration without the use of an effective charge, which could be considered as a significant achievement of the present approach.
Development of Aerobic Microbial Granules to Enhance the Performance of Activated Sludge Technology for Wastewater Treatment Application
Authors: Setianingsih Nanik Indah , Yuliasni Rustiana
Published: June 2020

Batik industry is one of textile industries in Indonesia generally in small and medium scale and has not good management of by-products in the form of wastewater. Wastewater from batik industry consist of complex and toxic pollutants hence need to be treated in order to support the development of environmentally friendly sustainable industry. Some researches have treated batik wastewater using conventional biological treatment such as anaerobic and activated sludge but optimal results have not been obtained. This research aims to develop a compact aerobic microbial granule with good endurance, which also rich in carbon and nutrient oxidizer bacteria to treat batik wastewater. Sequencing Batch Reactor (SBR) with volume of 8 L fed with Acetate (COD = 900-1000mg/L), then aerated for 180 minutes. Settling time variation was from 20 to 3 minutes, with 50% liquid withdrawal. In the 4 weeks operation there is increasing of MLVSS reached on 4760 mg/L with COD removal reach on 91,94%. The depletion of dissolved oxygen take effect on decreasing of MLVSS and COD removal.
Evaluation of Plant Structure in Urban Lake Ecosystem and Their Performance in Treatment Wetland Systems (TWS) to Maintain Lake Water Quality in Megacity Jakarta, Indonesia
Authors: Henny Cynthia , Kurniawan Riky
Published: June 2020

Urban lakes have become important city landscape to help maintaining the balance of hydrology (groundwater and surface) and ecology in urban ecosystem. Due to experiencing encroachment and severe pollution problems, the lakes require urgent handling and management. One of the promising alternative solutions of lake restoration and management is applying ecosystem-based approaches and/or green technology such as treatment wetland systems using plants. This paper will review various types of tropical plants (terrestrial and aquatic plants) and evaluate their role in maintaining urban lake water quality in megacity Jakarta and their performance in treatment wetland systems from our previous and on-going studies. Plants with more important role to contribute to improve lake water quality are the submerged and emergent plants. The most common and robust types of aquatic plants in less abundance and balanced plant structure and composition at the lake shoreline and littoral area with controlled submerged plants and no indication of invasive species give better lake water quality of urban lakes. The most robust type of aquatic plants and few types of terrestrial plants studied could give significant nutrient and solids removal efficiency in both constructed and floating treatment wetland systems. Using plants with ecosystem-based approaches according to plant structure at the lake surroundings and in the treatment wetland systems could contribute to maintain better urban lake water quality.
The Use of Greywater for Hydroponics Plant in Griya Katulampa Bogor City
Authors: Widiyanti Astrini , Arifin Hadi Susilo , Arifjaya Nana Mulyana
Published: June 2020

The daily activities of the community in Griya Katulampa which are washing clothes, cooking, and activities in the bathroom produce greywater. Greywater from the activity directly flows to the Ciliwung River. This has the potential to cause pollution in river water bodies. The purpose of this paper wasto publish the results of research on the impact of the use of filtered greywater for hydroponic plants. This study used experimental methods in the field to build bioretention demonstration plot that is used to filter greywater for hydroponic media of various types of leaf vegetable plants. Based on the results of the study, the use of individual greywaterwas 171.2 litres/person/day. From the results of the observations, it was shown that hydroponic growth at 4 weeks (harvesting time) of the highest productivitywerewater spinach (96.9%), lettuce (75.0%), and spinach (51.5%). Water spinach as a potential plant at 4 weeks had an average growth rate of 31 cm high, 2 stems, 30 leaves. Filter media used to produce the highest productivity of water spinach on the leaf part was the combination media of active charcoal-cyperus. Leaf is a part of water spinach plant that is commonly consumed by the community.
Assessing urban water security: case study Jakarta
Authors: Tarigan S D , Mahera S
Published: June 2020

Water security is the availability of freshwater with sufficient quantity and quality at the right time. The water security is a prerequisite for economic security, as well as for socioecology and human security. The concept of water security has received increased attention over the past decade, in both policy and academic cycles. The assessment of water security can be carried out in city, watershed and country scale. The aim of this study is to calculate water security index at the city scale using Jakarta as case study and then to compare the index with another selected city in ASEAN region. When calculated temporally, the water security index can be used to evaluate the improvement of water infrastructure in a city. The assessment was carried using five dimensions and eight indicators, each one assigned with equal weights. The following dimensions were used: a) Domestic water security, b) Economic water security, c) Environmental water security, d) Water-related disaster, e) Governance and management. The selected indicators were water supply access, water quality, economic value of water, extent of water treatment, water quality of natural water bodies, impact of disaster, budget for water management, technological interventions. Based on the assessment, Jakarta is classified as low-medium water security. The dimensions that need strong improvement to increase water security index of Jakarta are environmental water security, water related disaster, and governance and management. The domestic water security was in the medium level but it should be further improved to secure the water, and for economic water security, it was in the very high level in water security. Comparing to Bangkok City, the water security index of Jakarta is slightly lower.
The importance of remnant vegetation coverage along riverbank in supporting urban river naturalization in Bogor City, Indonesia
Authors: Mosyaftiani Amarizni , Arifin Hadi Susilo , Kaswanto
Published: June 2020

Human disturbances in urban river landscape and its riverbank cannot be avoided. The construction of buildings and other infrastructure are among the human disturbances which cause a serious decline in urban riverbank quality so that influencing the stability of its landscape ecological cycle. Exploration of vegetated urban riverbank in Indonesia, especially in Bogor City is very important to save its existence in supporting the naturalization of the Ciliwung River. This study aims to estimate the remnant vegetated urban riverbank along the Ciliwung River and estimate the value of landscape/ecosystem services along the riverbank in the Bogor City. This research was carried out by taking four sample locations of the 250 meters and 15 meters wide at the right and the left of the riverbank using aerial photography and processed with ArcGIS software. Then, the land cover delineation and ecosystem services of the four sample locations are estimated by random point sampling method as many as 500 points for each sample location using i-Tree Assessment. The results of this study indicated that vegetation cover along the riverbank in Bogor City is 62% or 300,443 m2 ± 1733.96 m2. The advantages of landscape service for tree vegetation along the Ciliwung riverbank in Bogor City, converted into economic value, is equal to IDR 178,272,333. The landscape ecological function of riparian vegetation has a large role in absorbing pollutant gases in cities, storing carbon in biomass and dust absorption as much as converted into these economic values. Protection and conservation of the remnant vegetated urban riverbank needs to be conducted with various stakeholders so that the value of landscape services can be increased optimally in achieving success of river naturalization for sustainable urban water system in Bogor City.
Changes in the Land Use Pattern of the Parat River Subwatershed, Salatiga, Central Java
Authors: Mulia Seviana , Jumari  , Utami Sri , Soeprobowati Tri Retnaningsih
Published: June 2020

Rawapening Lake is one of the 15 national priority lakes and a pilot project of the GERMADAN (Gerakan Penyelamatan Danau) Indonesian. The main problems of Rawapening are eutrophication and sedimentation from water catchment area (agriculture, livestock, domestic and industrial waste) and from the water body itself with various changes in land use patterns that occur in the surrounding rivers. Parat River is one of 9 rivers that empties into Rawapening. This study aims to analyze patterns of land use change in the Parat River sub-watershed in the last 25 years, using geographic information systems (GIS) remote sensing applications. The time series used were 1994, 2000, 2003, 2009, 2014 and 2018. The data was interpreted based on the types of land cover and how the changes occurred during that time period. There are seven types of land cover identified in this study. The area increases of plantation land types (1.12%) and built-up land (5.69%), is in line with the decrease in the area of Rice field type (7.78%), savanna (0.44%), swamp grass (0.40%), open land (0.25%) and body of water (0.01%). Changes in the pattern of land use in the Parat River Sub-watershed, in line with the increase in the amount of contamination carried and then will affect the lake where it empties, which is Rawapening.
Religious based water management campaigns for sustainable development: prospects and challenges
Authors: Muhammad Sheriffdeen , Amal S
Published: June 2020

A raising awareness of the environmental issues associated with natural resources utilization and degradation has been grown since the past few decades. Depletion of the renewable and non-renewable environmental resources has occurred mainly as a result of unsustainable utilization. This paper presents the idea of water conservation and utilization campaigns based on Islamic principles, since Islamic religion still exerts great influence on societies and because water plays an extremely pivotal role within Islam. Awareness campaigns and water conservation programmes based on religious principles have proved very useful, beneficial and cost effective in different areas of the Muslim world. Teachings regarding practical and correct use of water in the Islamic religion were highlighted, applicable examples from some Muslim countries including the challenges were also highlighted, and it was concluded that public awareness campaigns based on Islamic principles, can be a powerful yet cost effective tool to supplement other water conservation and management policies.
Assessment of Groundwater Vulnerability Using GOD Method
Authors: Sukmawati Rukmana Bantar Tyas , Bargawa Waterman Sulistyana , Cahyadi Tedy Agung
Published: June 2020

Mining activities can affect the availability of groundwater both in quantity and quality. Example of mining activities that can cause pollution are overburden stockpiling, construction of haul road facilities and infrastructure, coal processing and stockpiling activities, workshops, and domestic waste disposal. One effort to maintain groundwater is to analyze the groundwater vulnerability. This research was conducted to analyze the vulnerability of groundwater to pollution of PT. X in Balangan, South Kalimantan. The method used to assess groundwater vulnerability in this study is the GOD method (groundwater occurrence or aquifer type, overall lithology of aquifer, and depth of groundwater). Determining the groundwater vulnerability class with this method will be based on three parameters, namely type of aquifer, lithology or rock type, and depth of groundwater table. The GOD method divides each parameter into several classes in consonance to the weight of each parameter corresponding to the effect on groundwater vulnerability. Based on the results of the analysis, it is indicated that the area of PT. X is included in the category of negligible and moderate vulnerability. The results of the analysis can be used for recommendations for groundwater management in the study area. The GOD method can also be used to determine groundwater vulnerability in urban areas that have different land uses.
Communication Network Structure in Developing Water-Friendly Behavior in Dense Community
Authors: Pandjaitan Nurmala K , Lasinta Megafirmawanti
Published: June 2020

Water is the main element for the survival of human life and other living things. The availability of water is not only the responsibility of the government but also involves the community in its preservation through water-friendly behavior in the community. In fact, many residents have not yet realized the importance of saving water and maintaining water sources around it. One way to improve water-friendly behavior is through a process of communication between citizens in the community. This study aimed to analyze the structure of communication networks among citizens in an effort to build water-friendly behavior in densely populated communities that experience limited water. Primary data was obtained through surveys on 50 respondents who were equipped with qualitative data through interviews. The data were analyzed by the sociometric method and showed that the structure of the communication network in establishing water-friendly behavior was in the form of radial personal networks where the information center in the community was located in certain people. In this structure there are individuals who act as star actors. They are individuals with important positions in the community who act as Chair of RT and Posyandu Cadres. Most of the star in the network are women. The network structure formed also shows the existence of isolated individuals. People who are isolates are individuals who are elderly (above 50 years) with a solid level of activity (trading). They have the opinion that environmental management in the community is only incidental and unsustainable. In addition there are bridges in the network structure, namely individuals who become members in more than one click or group in the community. The process of interaction between individuals in the community in an effort to build water-friendly behavior is mostly done through face to face communication in daily conversations and at formal meetings such as RT meetings and socialization from the government.
Willingness To Pay and Consumption Characteristics Of Drinking Water to the Housholds in Katulampa Village, City of Bogor
Authors: Syaukat Yusman , Maryani Asih
Published: June 2020

Katulampa Village has a variety of potential water resources with relatively good quality. The existence of a variety of water provides an alternative to the community to use clean water. With the increasing number of population and water needs on the one hand, while on the other hand the quantity and quality of water resources is relatively decreasing, the optimal management of water resources to meet various community needs is increasingly important. The objectives of this study are to identify the patterns of community water consumption in the Katulampa Village, to estimate household expenditure for water consumption, and to estimate the value of household willingness to pay (WTP) for water. This research uses descriptive analysis, expenditure analysis method, and contingent valuation method. The results indicated that households in the Katulampa Village consume on average 23.9 m3/month, which comes from various water sources, namely PDAM water, wells, rivers, springs, and seepage water. Bottled drinking water (bottled water) and refilled water are consumed by communities specially to meet the needs of some drinking water. The proportion of expenditure for consumption of bottled water and refill water were relatively low compared to the average income of the people inside and outside Griya Katulampa Housing (GKH). Household expenditure for bottled water and refilled water is relatively high. The estimated average WTP for improved PDAM piped water is Rp 4,414/m3. Seepage water is still consumed by some people, although its use is limited to non-consumption activities.
Consumption Patterns, Perception, And Economic Value of Drinking Water to the Households in Pulogelis, City of Bogor
Authors: Syaukat Yusman , Anggraini Arum
Published: June 2020

The high population and economic activities in Bogor City have caused pressures on natural resources and the environment, and resulted in soil and water pollution. Community in the PuloGeulis Village is one of the areas in the city of Bogor whose face the problems of ground water and poor sanitation conditions. As a result, people must allocate a portion of their incomes to consume piped water (PDAM water), bottled drinking water (AMDK), and refilled water. The purpose of this study is to identify sources of drinking water in meeting the needs of clean water for the people of Kampung PuloGeulis, to estimate the amount of expenditure for clean water consumption, and to estimate willingness to pay (WTP) of the community in the provision of improved clean water from the PDAM. Data analysis methods include descriptive analysis, income and expenditure analysis, and contingent valuation method. The results showed that the PuloGeulis community had four main water sources and produced five patterns of combined use of water. Total expenditure for clean water consumption is still relatively low i.e., about 4% of the average household income. People consume bottled water and refilled water because, it is perceived, that the quality of PDAM water is lower than alternative water sources. This has resulted in higher willingness to pay when there is an improvement in the water supply system through the PDAM. The estimated value of household WTP is quite high, around Rp 4,573/m3 for household in category R3. The community has felt the impact of waste pollution in the forms of smell and contamination of the surrounding land and water, so they proposed several environmental improvement programs in the Pulo Geulis area.
Flow control by pile-group groynes used for riverbank instability management
Authors: Safie O , Tominaga A
Published: June 2020

Smooth reduction of velocity from the mainstream to the bank is a desirable attempt when using a groyne for riverbank protection purpose. This can be achieved by applying modifications to groyne permeability or layout. In this study, the effects of different pile-group groynes on the flow deceleration were investigated experimentally. Different aspects including pile density, arrangement, row spacing and effects on the long downstream were considered. The results show that the pile arrangement pattern is an important factor on the control of flow magnitude and pattern behind a pile-group groyne. A gradual and smooth velocity reduction from the mainstream to the bank can be obtained by changing the arrangement of piles in a pile-group groyne.
Pidgin play: Linguistic subversion on Chinese-run construction sites in Ethiopia
Authors: Driessen Miriam
Published: June 2020

The Chinese-run construction sites that have emerged across the Ethiopian landscape over the past two decades have given rise to a pidgin—a contact language that facilitates communication between Chinese managers and the Ethiopian labourers under their direction. By unravelling the nature of this pidgin, including its lexicon, syntax, and semantics, this article discusses the power dynamics in Ethiopian–Chinese encounters through the lens of language. A prototypical contact language at first blush, the pidgin spoken on Chinese road projects in Ethiopia is different from pidgins that emerged in colonial Africa. Its structure and use reveal that power relations between Chinese management and Ethiopian rank and file are less asymmetrical than often portrayed. As a site of contestation as much as collaboration, pidgin has in fact become one of the domains in which power is negotiated. By hijacking words and manipulating their meanings, Ethiopian workers play with pidgin in an attempt to confront expatriate management and challenge the sociopolitical asymmetries that the growing Chinese presence in their country has brought forth.
The (self) protection of civilians in South Sudan: Popular and community justice practices
Authors: Rhoads Emily Paddon , Sutton Rebecca
Published: June 2020

Over the past decade, a body of scholarship on civilian self-protection (CSP) has emerged, advancing understandings of civilian agency in war. In this article, we argue that CSP has been conceptualized in a narrow manner, reflecting the nascent status of the field. Scholars have focused on responses to threats directly related to the dynamics of conflict, physical in nature, and caused by the presence of armed groups. Using the case study of the Protection of Civilians (PoC) sites in South Sudan and drawing on over 150 interviews, we identify one type of protective response neglected in the literature: community and popular justice. Although the PoC sites provide a measure of protection, residents face a range of daily threats that are indirectly related to the conflict, such as crime. In this context, community justice emerged as a natural response, an overlooked yet vital form of CSP that addresses immediate protection needs and fulfills a social ordering function. By conceiving of justice in this way, this article aims to deepen understanding of civilian agency and start a conversation with scholars and practitioners about the boundaries of (self) protection.
The clinical usefulness of muscle mass and strength measures in older people: a systematic review
Authors: Lunt Eleanor , Ong Terence , Gordon Adam L , Greenhaff Paul L , Gladman John R F
Published: June 2020

Background

sarcopenia is the loss of muscle mass and quality and is diagnosed using measures of muscle strength, size and mass. We evaluated the literature on whether sarcopenia measures are predictive of motor outcomes in older people in clinical settings.

Methods

electronic databases (MEDLINE Ovid, EMBASE, CINAHL and Web of Science) were searched for articles on measures of muscle mass, volume, thickness or strength, in older people in clinical settings, which reported cross-sectional or longitudinal associations with motor outcomes. Clinical cohorts included geriatric medical inpatients and outpatients, patients with hip fracture, geriatric rehabilitation and care home residents. Motor outcomes were mobility, falls, balance and activities of daily living (ADL). Due to high study heterogeneity, standardised mean differences were used to compare strength of associations.

Results

in total, 83 articles were identified. The most frequently studied measures were grip strength (47 studies), knee extension strength (21 studies) and bioelectrical impedance analysis (18 studies). Handgrip strength (HGS) had evidence for cross-sectional associations with mobility (14 of 16 studies, 2,088 participants), balance (6 of 6 studies, 1,177 participants) and ADL independence (10 of 11 studies, 3,228 participants), and evidence of longitudinal associations with mobility (3 of 3 studies, 883 participants) and ADL independence (7 of 10 studies, 1,511 participants). There was no conclusive evidence for association with falls.

Conclusions

HS was the most studied measure and was associated with mobility, balance and ADL outcomes. There was a paucity of studies, particularly with longitudinal follow-up, measuring muscle mass, volume or thickness using gold-standard approaches.
Antihypertensive Drugs and Risk of Cancer: Between Scylla and Charybdis
Authors: Sanidas Elias , Velliou Maria , Papadopoulos Dimitrios , Fotsali Anastasia , Iliopoulos Dimitrios , Mantzourani Marina , Toutouzas Konstantinos , Barbetseas John
Published: June 2020

Antihypertensive drugs namely angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta blockers, and diuretics are among the most clearly documented regimens worldwide with an overall cardioprotective benefit. Given that malignancy is the second leading cause of mortality, numerous observational studies aimed to investigate the carcinogenic potential of these agents with conflicting results. The purpose of this review was to summarize current data in an effort to explore rare side effects and new mechanisms linking antihypertensive drugs with the risk of developing cancer.
Recent advances of automated methods for searching and extracting genomic variant information from biomedical literature
Authors: Lee Kyubum , Wei Chih-Hsuan , Lu Zhiyong
Published: June 2020

Motivation

To obtain key information for personalized medicine and cancer research, clinicians and researchers in the biomedical field are in great need of searching genomic variant information from the biomedical literature now than ever before. Due to the various written forms of genomic variants, however, it is difficult to locate the right information from the literature when using a general literature search system. To address the difficulty of locating genomic variant information from the literature, researchers have suggested various solutions based on automated literature-mining techniques. There is, however, no study for summarizing and comparing existing tools for genomic variant literature mining in terms of how to search easily for information in the literature on genomic variants.

Results

In this article, we systematically compared currently available genomic variant recognition and normalization tools as well as the literature search engines that adopted these literature-mining techniques. First, we explain the problems that are caused by the use of non-standard formats of genomic variants in the PubMed literature by considering examples from the literature and show the prevalence of the problem. Second, we review literature-mining tools that address the problem by recognizing and normalizing the various forms of genomic variants in the literature and systematically compare them. Third, we present and compare existing literature search engines that are designed for a genomic variant search by using the literature-mining techniques. We expect this work to be helpful for researchers who seek information about genomic variants from the literature, developers who integrate genomic variant information from the literature and beyond.
Phenotype-specific differences in polygenicity and effect size distribution across functional annotation categories revealed by AI-MiXeR
Authors: Shadrin Alexey A , Frei Oleksandr , Smeland Olav B , Bettella Francesco , O'Connell Kevin S , Gani Osman , Bahrami Shahram , Uggen Tea K E , Djurovic Srdjan , Holland Dominic , Andreassen Ole A , Dale Anders M
Published: June 2020

Motivation

Determining the relative contributions of functional genetic categories is fundamental to understanding the genetic etiology of complex human traits and diseases. Here, we present Annotation Informed-MiXeR, a likelihood-based method for estimating the number of variants influencing a phenotype and their effect sizes across different functional annotation categories of the genome using summary statistics from genome-wide association studies.

Results

Extensive simulations demonstrate that the model is valid for a broad range of genetic architectures. The model suggests that complex human phenotypes substantially differ in the number of causal variants, their localization in the genome and their effect sizes. Specifically, the exons of protein-coding genes harbor more than 90% of variants influencing type 2 diabetes and inflammatory bowel disease, making them good candidates for whole-exome studies. In contrast, <10% of the causal variants for schizophrenia, bipolar disorder and attention-deficit/hyperactivity disorder are located in protein-coding exons, indicating a more substantial role of regulatory mechanisms in the pathogenesis of these disorders.

Availability and implementation

The software is available at: https://github.com/precimed/mixer.

Supplementary information

Supplementary data are available at Bioinformatics online.
Phenotypic diversity and its relationship to reproductive potential in changing social contexts in a lizard model
Authors: López Juri Guadalupe , Rossi Nicola , Chiaraviglio Margarita , Cardozo Gabriela
Published: June 2020

Phenotype in lizards is related to reproductive function, and hence to reproductive output. Besides the intraspecific diversity in phenotypes, their temporal variation throughout the reproductive season in relation to the variation of social contexts builds extra complexity into sexual selection scenarios. One useful model for understanding phenotypic diversity dynamics is Tropidurus spinulosus because it presents sexual dimorphism in different phenotypic traits, dichromatism in regions related to reproductive behaviour, and it has intense social reproductive interactions. We aimed to evaluate how the reproductive and phenotypic traits of individuals vary with changing social contexts, and how intrasexual phenotypic diversity and reproductive potential are explained by the phenotypic traits. In this study, we used data obtained during four consecutive breeding seasons (2015–2018) in a wild population. The social context, characterized according to the operational sex ratio, varied between months and, therefore, some phenotypic and reproductive traits also varied. We found that body robustness and chromatic diversity were the main sources of phenotypic diversity and were related to reproductive traits in both sexes. Our results help to understand the dynamics and reproductive implications of phenotypic diversity in changing social contexts in a lizard social model.
Gene therapy for global brain diseases: one small step for mice, one giant leap for humans
Authors: Rahim Ahad A , Gissen Paul
Published: June 2020

This scientific commentary refers to ‘Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy’, by Yoon et al. (doi:10.1093/brain/awaa161).
Loss of supervillin causes myopathy with myofibrillar disorganization and autophagic vacuoles
Authors: Hedberg-Oldfors Carola , Meyer Robert , Nolte Kay , Abdul Rahim Yassir , Lindberg Christopher , Karason Kristjan , Thuestad Inger Johanne , Visuttijai Kittichate , Geijer Mats , Begemann Matthias , Kraft Florian , Lausberg Eva , Hitpass Lea , Götzl Rebekka , Luna Elizabeth J , Lochmüller Hanns , Koschmieder Steffen , Gramlich Michael , Gess Burkhard , Elbracht Miriam , Weis Joachim , Kurth Ingo , Oldfors Anders , Knopp Cordula
Published: June 2020

The muscle specific isoform of the supervillin protein (SV2), encoded by the SVIL gene, is a large sarcolemmal myosin II- and F-actin-binding protein. Supervillin (SV2) binds and co-localizes with costameric dystrophin and binds nebulin, potentially attaching the sarcolemma to myofibrillar Z-lines. Despite its important role in muscle cell physiology suggested by various in vitro studies, there are so far no reports of any human disease caused by SVIL mutations. We here report four patients from two unrelated, consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Muscle biopsies showed complete loss of large supervillin isoforms in muscle fibres by western blot and immunohistochemical analyses. Light and electron microscopic investigations revealed a structural myopathy with numerous lobulated muscle fibres and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network. Autophagic vacuoles, as well as frequent and extensive deposits of lipoproteins, including immature lipofuscin, were observed. Several sarcolemma-associated proteins, including dystrophin and sarcoglycans, were partially mis-localized. The results demonstrate the importance of the supervillin (SV2) protein for the structural integrity of muscle fibres in humans and show that recessive loss-of-function mutations in SVIL cause a distinctive and novel myopathy.
The FUS about SFPQ in FTLD spectrum disorders
Authors: Patani Rickie
Published: June 2020

This scientific commentary refers to ‘Aberrant interaction between FUS and SFPQ in neurons of a wide range of FTLD spectrum diseases’, by Ishigaki etal. (doi:10.1093/brain/awaa196).
Aggresome-Like Formation Promotes Resistance to Proteotoxicity in Cells from Long-Lived Species
Authors: Sunchu Bharath , Riordan Ruben T , Yu Zhen , Almog Ido , Dimas-Munoz Jovita , Drake Andrew C , Perez Viviana I
Published: June 2020

The capacity of cells to maintain proteostasis declines with age, causing rapid accumulation of damaged proteins and protein aggregates, which plays an important role in age-related disease etiology. While our group and others have identified that proteostasis is enhanced in long-lived species, there are no data on whether this leads to better resistance to proteotoxicity. We compared the sensitivity of cells from long- (naked mole rat [NMR]) and short- (Mouse) lived species to proteotoxicity, by measuring the survival of fibroblasts under polyglutamine (polyQ) toxicity, a well-established model of protein aggregation. Additionally, to evaluate the contribution of proteostatic mechanisms to proteotoxicity resistance, we down-regulated a key protein of each mechanism (autophagy—ATG5; ubiquitin-proteasome—PSMD14; and chaperones—HSP27) in NMR fibroblasts. Furthermore, we analyzed the formation and subcellular localization of inclusions in long- and short-lived species. Here, we show that fibroblasts from long-lived species are more resistant to proteotoxicity than their short-lived counterparts. Surprisingly, this does not occur because the NMR cells have less polyQ82 protein aggregates, but rather they have an enhanced capacity to handle misfolded proteins and form protective perinuclear and aggresome-like inclusions. All three proteostatic mechanisms contribute to this resistance to polyQ toxicity but autophagy has the greatest effect. Overall, our data suggest that the resistance to proteotoxicity observed in long-lived species is not due to a lower level of protein aggregates but rather to enhanced handling of the protein aggregates through the formation of aggresome-like inclusions, a well-recognized protective mechanism against proteotoxicty.
An Alu-mediated duplication in NMNAT1, involved in NAD biosynthesis, causes a novel syndrome, SHILCA, affecting multiple tissues and organs
Authors: Bedoni Nicola , Quinodoz Mathieu , Pinelli Michele , Cappuccio Gerarda , Torella Annalaura , Nigro Vincenzo , Testa Francesco , Simonelli Francesca ,   TUDP (Telethon Undiagnosed Disease Program), Corton Marta , Lualdi Susanna , Lanza Federica , Morana Giovanni , Ayuso Carmen , Di Rocco Maja , Filocamo Mirella , Banfi Sandro , Brunetti-Pierri Nicola , Superti-Furga Andrea , Rivolta Carlo
Published: June 2020

We investigated the genetic origin of the phenotype displayed by three children from two unrelated Italian families, presenting with a previously unrecognized autosomal recessive disorder that included a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability and Leber congenital amaurosis (SHILCA), as well as some brain anomalies that were visible at the MRI. Autozygome-based analysis showed that these children shared a 4.76 Mb region of homozygosity on chromosome 1, with an identical haplotype. Nonetheless, whole-exome sequencing failed to identify any shared rare coding variants, in this region or elsewhere. We then determined the transcriptome of patients’ fibroblasts by RNA sequencing, followed by additional whole-genome sequencing experiments. Gene expression analysis revealed a 4-fold downregulation of the gene NMNAT1, residing indeed in the shared autozygous interval. Short- and long-read whole-genome sequencing highlighted a duplication involving 2 out of the 5 exons of NMNAT1 main isoform (NM_022787.3), leading to the production of aberrant mRNAs. Pathogenic variants in NMNAT1 have been previously shown to cause non-syndromic Leber congenital amaurosis (LCA). However, no patient with null biallelic mutations has ever been described, and murine Nmnat1 knockouts show embryonic lethality, indicating that complete absence of NMNAT1 activity is probably not compatible with life. The rearrangement found in our cases, presumably causing a strong but not complete reduction of enzymatic activity, may therefore result in an intermediate syndromic phenotype with respect to LCA and lethality.
Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies
Authors: Cai Na , Choi Karmel W , Fried Eiko I
Published: June 2020

With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now is whether recently discovered variants describe the etiology of a single disease entity. There are a myriad of ways to measure and operationalize depression severity, and major depressive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-5 can manifest in more than 10 000 ways based on symptom profiles alone. Variations in developmental timing, comorbidity and environmental contexts across individuals and samples further add to the heterogeneity. With big data increasingly enabling genomic discovery in psychiatry, it is more timely than ever to explicitly disentangle genetic contributions to what is likely ‘depressions’ rather than depression. Here, we introduce three sources of heterogeneity: operationalization, manifestation and etiology. We review recent efforts to identify depression subtypes using clinical and data-driven approaches, examine differences in genetic architecture of depression across contexts, and argue that heterogeneity in operationalizations of depression is likely a considerable source of inconsistency. Finally, we offer recommendations and considerations for the field going forward.
The optimal age of vaccination against dengue in Brazil based on serotype-specific forces of infection derived from serological data
Authors: Maier Sandra B , Massad Eduardo , Amaku Marcos , Burattini Marcelo N , Greenhalgh David
Published: June 2020

In this paper, we study a single serotype transmission model of dengue to determine the optimal vaccination age for Dengvaxia. The transmission dynamics are modelled with an age-dependent force of infection. The force of infection for each serotype is derived from the serological profile of dengue in Brazil without serotype distinction and from serotype-specific reported cases. The risk due to an infection is measured by the probability of requiring hospitalization based on Brazilian Ministry of Health data. The optimal vaccination age is determined for any number and combination of the four distinct dengue virus serotypes DENv1–4. The lifetime expected risk is adapted to include antibody dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections. The risk is assumed to be serostatus-dependent. The optimal vaccination age is computed for constant, serostatus-specific vaccine efficacies. Additionally, the vaccination age is restricted to conform to the licence of Dengvaxia in Brazil and the achievable and minimal lifetime expected risks are compared. The optimal vaccination age obtained for the risk of hospitalization varies significantly with the assumptions relating to ADE and cross-immunity. Risk-free primary infections lead to higher optimal vaccination ages, as do asymptomatic third and fourth infections. Sometimes vaccination is not recommended at all, e.g. for any endemic area with a single serotype if primary infections are risk-free. Restricting the vaccination age to Dengvaxia licensed ages mostly leads to only a slightly higher lifetime expected risk and the vaccine should be administered as close as possible to the optimal vaccination age.
A meropenem pharmacokinetics model in patients with haematological malignancies
Authors: Contejean A , Jaffrelot L , Benaboud S , Tréluyer J -M , Grignano E , Willems L , Gauzit R , Bouscary D , Gana I , Boujaafar S , Kernéis S , Hirt D
Published: June 2020

Background

Optimal dosing of antibiotics is critical in immunocompromised patients suspected to have an infection. Data on pharmacokinetics (PK) of meropenem in patients with haematological malignancies are scarce.

Objectives

To optimize dosing regimens, we aimed to develop a PK population model for meropenem in this population.

Methods

Patients aged ≥18 years, hospitalized in the haematology department of our 1500 bed university hospital for a malignant haematological disease and who had received at least one dose of meropenem were eligible. Meropenem was quantified by HPLC. PK were described using a non-linear mixed-effect model and external validation performed on a distinct database. Monte Carlo simulations estimated the PTA, depending on renal function, duration of infusion and MIC. Target for free trough concentration was set at >4× MIC.

Results

Overall, 88 patients (181 samples) were included, 66 patients (75%) were in aplasia and median Modification of Diet in Renal Disease (MDRD) CLCR was 117 mL/min/1.73 m2 (range: 35–359). Initial meropenem dosing regimen ranged from 1 g q8h to 2 g q8h over 30 to 60 min. A one-compartment model with first-order elimination adequately described the data. Only MDRD CLCR was found to be significantly associated with CL. Only continuous infusion achieved a PTA of 100% whatever the MIC and MDRD CLCR. Short duration of infusion (<60 min) failed to reach an acceptable PTA, except for bacteria with MIC < 0.25 mg/L in patients with MDRD CLCR below 90 mL/min/1.73 m2.

Conclusions

In patients with malignant haematological diseases, meropenem should be administered at high dose (6 g/day) and on continuous infusion to reach acceptable trough concentrations.
Population pharmacokinetic evaluation and optimization of amikacin dosage regimens for the management of mycobacterial infections
Authors: Siebinga Hinke , Robb Fiona , Thomson Alison H
Published: June 2020

Background

There is limited information on amikacin pharmacokinetics (PK) and dose requirements in patients with mycobacterial infections.

Objectives

To conduct a population PK analysis of amikacin data from patients with mycobacterial infections and compare predicted concentrations from standard and modified dosage guidelines with recommended target ranges.

Methods

A population PK model was developed using NONMEM. Cmax, Cmin, concentration 1 h post-infusion (C1h) and AUC0–24 using 15 mg/kg daily (once daily), the WHO table, 25 mg/kg three times weekly (TTW) and modified guidelines were compared using Monte Carlo simulations of 1000 patients.

Results

Data were available from 124 patients (684 concentrations) aged 16–92 years. CL was 4.64 L/h per 100 mL/min CLCR; V was 0.344 L/kg. With once-daily regimens, Cmax was 35–45 mg/L in 30%–35% of patients and 35–50 mg/L in 46%–48%; C1h was 25–40 mg/L in 53%–59%. The WHO table produced high Cmax values in patients <60 kg and low in patients >75 kg. With TTW dosing, around 30% of Cmax values were 65–80 mg/L, 40% were 60–80 mg/L, and 48% of C1h were 45–65 mg/L. Increasing the dosage interval for patients with CLCR <50 mL/min reduced Cmin values >2 mg/L from 34% to 25% for once-daily dosing and from 18% to 13% for TTW. In patients whose Cmin was <2 mg/L, 82% of AUC0–24 values were 100–300 mg.h/L.

Conclusions

Standard amikacin dosing guidelines achieve low percentages of target concentrations for mycobacterial infections. Extending the dosing interval in renal impairment and widening target ranges would reduce the need for dose adjustment.
Sources of Uncertainty and Subjective Prices
Authors: Cappelli Veronica , Cerreia-Vioglio Simone , Maccheroni Fabio , Marinacci Massimo , Minardi Stefania
Published: June 2020

We develop a general framework to study source-dependent preferences in economic contexts. We behaviorally identify two key features. First, we drop the assumption of uniform uncertainty attitudes and allow for source-dependent attitudes. Second, we introduce subjective prices to compare outcomes across different sources. Our model evaluates profiles source-wise, by computing the source-dependent certainty equivalents; the latter are converted into the unit of account of a common source and then aggregated into a unique evaluation. By viewing time and location as instances of sources, we show that subjective discount factors and subjective exchange rates are emblematic examples of subjective prices. Finally, we use the model to explore the implications on optimal portfolio allocations and home bias.
Genetic Diversity and Population Structure of Dromedary Camel-Types
Authors: AlAskar Huda , Alhajeri Bader H , Almathen Faisal , Alhaddad Hasan
Published: June 2020

The dromedary camel is a unique livestock for its adaptations to arid-hot environments and its ability to provide goods under extreme conditions. There are no registries or breed standards for camels. Thus, named camel populations (i.e., camel-types) were examined for genetic uniqueness and breed status. Camel populations are generally named based on shared phenotype, country or region of origin, tribal ownership, or the ecology of their habitat. A dataset of 10 Short-Tandem Repeat markers genotyped for 701 individual camels from 27 camel-types was used to quantify genetic diversity within camel-types, compare genetic diversity across camel-types, determine the population genetic structure of camel-types, and identify camel-types that may represent true breeds. Summary statistics (genotyping call rate, heterozygosity, inbreeding coefficient FIS, and allelic frequencies) were calculated and population-specific analyses (pairwise FST, neighbor-joining tree, relatedness, Nei’s genetic distance, principal coordinate analysis [PCoA], and STRUCTURE) were performed. The most notable findings were 1) little variation in genetic diversity was found across the camel-types, 2) the highest genetic diversity measure was detected in Targui and the lowest was in Awarik, 3) camel-types from Asia (especially the Arabian Peninsula) exhibited higher genetic diversity than their counterparts in Africa, 4) the highest DeltaK value of population structure separated camel-types based on geography (Asia vs. Africa), 5) the most distinct camel-types were the Omani, Awarik, and the Gabbra, 6) camel-types originating from the same country did not necessarily share high genetic similarity (e.g., camel-types from Oman), and 7) camel-type names were not consistently indicative of breed status.