bluuebunny/crossref_metadata_2025 huggingface dataset:
Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication
Authors: Harrison Neale J , Connolly Elizabeth , Gascón Gubieda Alicia , Yang Zidan , Altenhein Benjamin , Losada Perez Maria , Moreira Marta , Sun Jun , Hidalgo Alicia
Published: February 2021

Understanding how injury to the central nervous system induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial neuron-glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related to the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Both loss and over-expression of ia-2 induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6) to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia and reprogrammes glia into neural stem cells for regeneration.
Emergence and propagation of epistasis in metabolic networks
Authors: Kryazhimskiy Sergey
Published: February 2021

Epistasis is often used to probe functional relationships between genes, and it plays an important role in evolution. However, we lack theory to understand how functional relationships at the molecular level translate into epistasis at the level of whole-organism phenotypes, such as fitness. Here, I derive two rules for how epistasis between mutations with small effects propagates from lower- to higher-level phenotypes in a hierarchical metabolic network with first-order kinetics and how such epistasis depends on topology. Most importantly, weak epistasis at a lower level may be distorted as it propagates to higher levels. Computational analyses show that epistasis in more realistic models likely follows similar, albeit more complex, patterns. These results suggest that pairwise inter-gene epistasis should be common, and it should generically depend on the genetic background and environment. Furthermore, the epistasis coefficients measured for high-level phenotypes may not be sufficient to fully infer the underlying functional relationships.
Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes
Authors: Stahley Sara N , Basta Lena P , Sharan Rishabh , Devenport Danelle
Published: February 2021

To orchestrate collective polarization across tissues, planar cell polarity (PCP) proteins localize asymmetrically to cell junctions, a conserved feature of PCP that requires the atypical cadherin Celsr1. We report that mouse Celsr1 engages in bothtrans- andcis-interactions, and organizes into dense and highly stable punctate assemblies. We provide evidence suggesting that PCP-mutant variant of Celsr1, Celsr1Crsh, selectively impairs lateralcis-interactions. Although Celsr1Crshmediates cell adhesion in trans, it displays increased mobility, diminishes junctional enrichment, and fails to engage in homophilic adhesion with the wild-type protein, phenotypes that can be rescued by ectopiccis-dimerization. Using biochemical and super-resolution microscopy approaches, we show that although Celsr1Crshphysically interacts with PCP proteins Frizzled6 and Vangl2, it fails to organize these proteins into asymmetric junctional complexes. Our results suggest mammalian Celsr1 functions not only as atrans-adhesive homodimeric bridge, but also as an organizer of intercellular Frizzled6 and Vangl2 asymmetry through lateral,cis-interactions.
Cycles, sources, and sinks: Conceptualizing how phosphate balance modulates carbon flux using yeast metabolic networks
Authors: Gupta Ritu , Laxman Sunil
Published: February 2021

Phosphates are ubiquitous molecules that enable critical intracellular biochemical reactions. Therefore, cells have elaborate responses to phosphate limitation. Our understanding of long-term transcriptional responses to phosphate limitation is extensive. Contrastingly, a systems-level perspective presenting unifying biochemical concepts to interpret how phosphate balance is critically coupled to (and controls) metabolic information flow is missing. To conceptualize such processes, utilizing yeast metabolic networks we categorize phosphates utilized in metabolism into cycles, sources and sinks. Through this, we identify metabolic reactions leading to putative phosphate sources or sinks. With this conceptualization, we illustrate how mass action driven flux towards sources and sinks enable cells to manage phosphate availability during transient/immediate phosphate limitations. We thereby identify how intracellular phosphate availability will predictably alter specific nodes in carbon metabolism, and determine signature cellular metabolic states. Finally, we identify a need to understand intracellular phosphate pools, in order to address mechanisms of phosphate regulation and restoration.
Visualizing traumatic brain injuries
Authors: Ekker Marc
Published: February 2021

Zebrafish larvae models can be used to study the link between seizures and the neurodegeneration that follows brain trauma.
Convergent organization of aberrant MYB complex controls oncogenic gene expression in acute myeloid leukemia
Authors: Takao Sumiko , Forbes Lauren , Uni Masahiro , Cheng Shuyuan , Pineda Jose Mario Bello , Tarumoto Yusuke , Cifani Paolo , Minuesa Gerard , Chen Celine , Kharas Michael G , Bradley Robert K , Vakoc Christopher R , Koche Richard P , Kentsis Alex
Published: February 2021

Dysregulated gene expression contributes to most prevalent features in human cancers. Here, we show that most subtypes of acute myeloid leukemia (AML) depend on the aberrant assembly of MYB transcriptional co-activator complex. By rapid and selective peptidomimetic interference with the binding of CBP/P300 to MYB, but not CREB or MLL1, we find that the leukemic functions of MYB are mediated by CBP/P300 co-activation of a distinct set of transcription factor complexes. These MYB complexes assemble aberrantly with LYL1, E2A, C/EBP family members, LMO2, and SATB1. They are organized convergently in genetically diverse subtypes of AML and are at least in part associated with inappropriate transcription factor co-expression. Peptidomimetic remodeling of oncogenic MYB complexes is accompanied by specific proteolysis and dynamic redistribution of CBP/P300 with alternative transcription factors such as RUNX1 to induce myeloid differentiation and apoptosis. Thus, aberrant assembly and sequestration of MYB:CBP/P300 complexes provide a unifying mechanism of oncogenic gene expression in AML. This work establishes a compelling strategy for their pharmacologic reprogramming and therapeutic targeting for diverse leukemias and possibly other human cancers caused by dysregulated gene control.
Effects of mixing two legume species at seedling stage under different environmental conditions
Authors: Elsalahy Heba , Bellingrath-Kimura Sonoko , Kautz Timo , Döring Thomas
Published: February 2021

While intercropping is known to have positive effects on crop productivity, it is unclear whether the effects of mixing species start at the early plant stage, that is, during germination. We tested whether the germination of two legume species, alsike clover and black medic, characterized by a contrasting response to water availability and temperature is affected by mixing. We set up four experiments in each of which we compared a 1:1 mixture against the two monocultures, and combined this with various other experimental factors. These additional factors were (i) varied seed densities (50%, 100% and 150% of a reference density) in two field trials in 2016 and 2017, (ii) varied seed densities (high and low) and water availability (six levels, between 25% and 100% of water holding capacity (WHC)) in a greenhouse pot trial, (iii) varied seed spacing in a climate chamber, and (iv) varied temperatures (12 °C, 20 °C and 28 °C) and water availability (four levels between 25% and 100% of WHC) in a climate chamber. Across all experiments, the absolute mixture effects (AME) on germination ranged between −9% and +11%, with a median of +1.3%. Within experiments, significant mixture effects were observed, but the direction of these effects was inconsistent. In the field, AME on germination was significantly negative at some of the tested seed densities. A positive AME was observed in the climate chamber at 12 °C, and the mean AME decreased with increasing temperature. Higher density was associated with decreased germination in the field, indicating negative interaction through competition or allelopathy, among seedlings. Our findings indicate that interaction among seeds in species mixtures may be ongoing during germination, but that the direction of the mixture effect is affected by complex interactions with abiotic and biotic factors.
Identification of candidate genes influencing anthocyanin biosynthesis during the development and ripening of red and white strawberry fruits via comparative transcriptome analysis
Authors: Zhao Fengli , Song Pan , Zhang Xiangfen , Li Gang , Hu Panpan , Aslam Ali , Zhao Xia , Zhou Houcheng
Published: February 2021

Strawberries are one of the most economically important berry fruits worldwide and exhibit colours ranging from white to dark red, providing a rich genetic resource for strawberry quality improvement. In the present study, we conducted transcriptome analyses of three strawberry cultivars, namely, ‘Benihoppe’, ‘Xiaobai’, and ‘Snow White’, and compared their gene expression profiles. Among the high-quality sequences, 5,049 and 53,200 differentially expressed genes (DEGs) were obtained when comparing the diploid and octoploid strawberry genomes and analysed to identify anthocyanin-related candidate genes. Sixty-five DEGs in the diploid genome (transcriptome data compared to the diploid strawberry genome) and 317 DEGs in the octoploid genome (transcriptome data compared to the octoploid strawberry genome) were identified among the three cultivars. Among these DEGs, 19 and 70 anthocyanin pathway genes, six and 42 sugar pathway genes, 23 and 101 hormone pathway genes, and 17 and 104 transcription factors in the diploid and octoploid genomes, respectively, correlated positively or negatively with the anthocyanin accumulation observed among the three cultivars. Real-time qPCR analysis of nine candidate genes showed a good correlation with the transcriptome data. For example, the expression of PAL was higher in ‘Benihoppe’ and ‘Xiaobai’ than in ‘Snow White’, consistent with the RNA-seq data. Thus, the RNA-seq data and candidate DEGs identified in the present study provide a sound basis for further studies of strawberry fruit colour formation.
Effects of Feeding Diets Containing Pearl Millet Supplemented with Enzyme on the Carcass and Haematological Values of Broiler Chicken
Authors: Edache John Amedu , Inyam Lydia , Edache Stephen Ejembi
Published: February 2021

Pearl millet, which is comparable to maize in terms of its metabolizable energy content is an identified potential replacement for maize in broiler diets. However, as the competition and price of maize continues to spike, the continuous need to completely replace maize in broiler diets is imperative. Therefore, the objectives of this study were to investigate the effects of feeding diets containing pearl millet supplemented with enzyme NatuzymeTM on the carcass characteristics and haematological values of broiler chickens. 150 two weeks-old broilers were randomly divided into 5 groups with 10 birds per pen translating into 10 birds per replicate and fed an isonitrogenous (23%CP) starter diet of control diet (A); 0% (B); 10% (C); 20% (D); 30.01% and (E) 37.41 % pearl millet. Similarly, an isonitrogenous (21%CP) finisher diet of control diet (A); 0% (B); 10.64% pearl millet (C); 21.28% (D); 31.92% and (E) 39.27 % of pearl millet for 6 weeks. The birds were randomly allotted to the diets in a completely randomized design with feed and water given ad libitum. With the exception of drumstick of birds fed diet D which was significantly lower than the other diets, the results showed that the carcass values (parameters) of broilers fed 100% pearl millet were similar or non-superior to the control group and the other diets. Similarly, blood parameters were not significantly different between groups. These results show that pearl millet supplemented with enzyme can replace maize in broiler diets without affecting carcass yields and haematological parameters.
Assessment of Livelihood Vulnerability of Fisherfolks in Coastal and Freshwater Fishing Communities of Ilaje in Ondo State
Authors: Omitoyin Siyanbola A. , Ogungbure Adeniyi P. , Osakuade Kemisola D.
Published: February 2021

The study assessed the livelihood vulnerability of fisherfolks in both coastal and freshwater fishing communities of Ilaje Local Government area of Ondo state, Nigeria. Structured questionnaires were used to collect information from 200 fisherfolks from both communities. Data were analyzed using the descriptive statistics, Livelihood Vulnerability Index data were aggregated using a composite index and differential vulnerabilities were compared. The results showed that majority of the fisherfolks from freshwater and coastal communities were below 46 years old, respondents from the freshwater communities were 95% male, 5% females while all (100%) respondents in the coastal communities were male with majority assenting to fishing as their primary occupation. The freshwater communities showed greater vulnerability on the socio-demographic profile (SDP) index than coastal communities (SDP freshwater 0.49;SDPcoastal communities 0.34). Freshwater also showed greater vulnerability on the livelihood strategies component (0.45) than coastal communities (0.40). The social networks indicators were the same for the two communities. The overall health vulnerability score for freshwater communities (0.46) was higher than that for coastal communities (0.44).  Also, the overall food vulnerability score for freshwater households (0.23) was greater than that of coastal community households (0.22). Freshwater households had a lower vulnerability score (0.03) for the water component than coastal communities (0.17). Based on the incidents of flooding, droughts, storms and erosion, households in the coastal communities (0.50) were more vulnerable to natural disasters than those in the freshwater communities (0.41). Overall, coastal communities had a higher Livelihood Vulnerability Index (LVI) than freshwater (0.357 versus 0.356).This logical approach may be used to monitor vulnerability, programs and resources to assist fisherfolks. Also, there should be enlightenment on how to mitigate the factors enhancing climate change while good infrastructure and aids be given to those who suffer losses due to climate change impacts.
Interaction Effect of Land Uses and Time on Some Water Transmission Properties and Fertility Status of an Ultisol in Imo State, Nigeria
Authors: Onyegbule U. O. , Eneje R. C. , Akagha N. U. , Ike S. G. I. , Okoro L. C.
Published: February 2021

The interaction of land use and time on some soil water transmission properties and fertility status of an Ultisol was examined. Results indicate that the texture of the soils ranged from sandy loamy to sandy clay loam and was unaffected by land use and time. The bulk density varied significantly across the land uses with the Sand mining site SM having the highest bulk density of 1.7 and 1.78 g/cm3 in the first and second years respectively. The Primary forest, PFL had the lowest BD of 1.50 and 1.78 g/cm3 in the first and second year of studies respectively. Similarly the percentage porosity varied significantly across the four land uses and has its highest value of 43.1 and 42.3% in the first PFL of the first and second year studies. Also the saturated hydraulic conductivity KSat and moisture content MC were significantly different across the four land uses, the Ksat was highest in the PFL in both first and second year of studies (17.2 and 14.7 cm/min), the least Ksat values of 6.70 and 5.88 cm/min occurred in the 1st year sand mining site SM. Similarly there was a significant difference (P>0.05) in the percentage organic matter OM, Total nitrogen N, available phosphorous P, exchangeable acidity, Percentage base saturation BS, and CEC across the land uses, however the total N was only significant in land uses PFL and not in the other land uses. Generally the soil quality indicators ranged from low to moderate in ratings and have affected productivity of recent in the area. Appropriate land uses that will restore the productive potentials of the soil should be adopted and sustained. Similarly the organic matter of the soils should be improved on as this will go a long way in improving appreciably the poor soil water transmission properties.
Sperm Lipid Peroxidation and Antioxidants Activities as Predictors of Pregnancy Outcomes after Density Gradient Centrifugation in Medical Assistance Procreation
Authors: Debbarh Hasnae , Aboulmaouahib Smahane , Jamil Malak , Mounaji Khadija , Sefrioui Omar , Louanjli Noureddine , Cadi Rachida
Published: February 2021

Aims: The purpose of this study was to assess the Density Gradient Centrifugation (DGC) effectiveness in spermatozoa selection by analyzing the oxidative stress profile and in pregnancy prediction outcomes of In Vitro Fertilization (IVF).

Study Design: This was a prospective study.

Place and Duration of Study: Department of Biology, laboratory of Physiopathology Molecular Genetic and Biotechnology. Ain Chock Faculty of Sciences, Hassan II University, Casablanca. And Anfa Fertility Center Private Clinic of in vitro fertilization and Endoscopic Surgery, Casablanca.

Methodology: We included 101 men patients subdivided into three groups. Group A with normal sperm parameters and a positive pregnancy; Group B with normal sperm parameters and a negative pregnancy; Group C with abnormal sperm parameters and a negative pregnancy. After DGC, lipid peroxidation (MDA) level, as well as the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT), were evaluated.

Results: Patients with normal and abnormal sperm parameters showed that MDA level, and antioxidant enzymes activities increased significantly from the pellet, to 80 %, and from 80% to 40% fractions. In addition, lipid peroxidation and enzymes activities levels were significantly lower in patients with positive pregnancy than in patients with negative pregnancy and especially those with abnormal spermatic parameters.

Conclusion: The DGC would select sperm not only motile and viable but with less oxidative stress. Moreover, the rate of lipid peroxidation and antioxidant enzyme activities could differentiate between patients with normal and abnormal spermatic parameters and between patients with positive and negative pregnancy outcome.
Distribution, Importance and Diseases of Soybean and Common Bean: A Review
Authors: Singh Gaurav , Dukariya Garima , Kumar Anil
Published: February 2021

The crops belonging to the family Leguminosae are the second to cereal crops of agricultural significance due to their high nutritional value. Soybean is native to East Asia and was originated in China while common bean is native to Central and Southern America originated in Peru. Both soybean and common bean are erect, bushy annual herbaceous plants growing up to 150 and 40 centimeters in height, respectively. They have enormous food and medicinal values. Soybean and common bean are important leguminous crops which are excellent source of high-quality proteins, minerals, vitamins, polyunsaturated fats, and other nutrients for both human and other animal feeds. Soybean is beneficial for weight loss, diabetics as dietary supplements, bone loss in women and minimizing cancer risks while common bean is useful for preventing constipation, lowering cholesterol levels and reducing the risk of heart diseases. Pests, pathogens and weeds cause harmful effect resulting in low production of both the legume crops. The present review focuses on the overview, different importance and diseases of soybean (Glycine max) and common bean (Phaseolus vulgaris). In addition, attention has been paid on various aspects of these two legumes namely taxonomy, morphological features, origin and distribution along with their pests and diseases.
Extraction, Purification and Characterization of Lycopene from Tomato (Cv Vijeta) Processing Industry Waste
Authors: Ranveer R. C. , Rathod N. B. , Debaje P. P. , Sahoo A. K.
Published: February 2021

Aim: The present study focused on extraction of lycopene from tomato processing industry waste, its purification and characterization by different methods. Lycopene is major carotenoid found in tomato.

Methodology: Different tomato parts like whole tomato, tomato peel and waste generated druing processing were also screened for lycopene content. The extracted lycopene was purified by crystallization method. The purified lycopene was characterized by the different methods live UV- spectroscopy, HPLC, FT-IR and NMR.

Results: Among the different parts of tomato the peel (377.19±1.13 µg/g) contain highest amount of lycopene than industrial waste (175.15±1.09 µg/g) and whole tomato (82.82±0.79). The crystallization method significantly purify the lycopene content which was clearly resulted in UV-spectroscopy, HPLC, FT-IR and NMR results.

Conclusion: This will be beneficial to the industry for purification and characterization of lycopene from tomato processing industry waste.
Prevalence of Typhoid Infection among Pregnant Women Attending Specialist Hospital Yola, Adamawa State, Nigeria
Authors: Kwala Kefas Hellamada , Asika Aminu Innocent
Published: February 2021

Typhoid fever is one of the major and common health problem worldwide. Typhoid fever caused by Salmonella typhi may be a cause of significant morbidity and mortality in both the mother and fetus in developing countries, where sanitation facilities, personal and food hygiene are inadequate. Thus, the present research was a cross-sectional study of Salmonella infection among pregnant women in Specialist Hospital Yola, Nigeria. The objectives of this study is to determine the prevalence of typhoid infection among pregnant women in Adamawa state in relation to age, educational level, occupation and location, explore factors associated with the infection and to provide information on its prevention and control strategies. Serological analyses (Widal test) and bacteriological analyses (stool culture) were carried out and compared among 313 participants. The results obtained showed that 209 (66.77%) of the participants were seropositive for typhoid fever, whereas 188 (60.06%) were positive based on bacteriological technique. Participants between age groups; 26-35 years old had the highest prevalence of 64.10%.There was no statistically significant difference (P>0.05) between the prevalence of typhoid fever among the various age groups of the pregnant women examined. In relation to Educational level, participants with Non-formal education had the highest prevalence of typhoid infection 75.00%. There was no statistically significant difference (P>0.05) between the prevalence of typhoid fever based on the educational level of the pregnant women examined.  Based on occupation of the participants, women who were involved in farming recorded the highest prevalence rate of 88.37%.There was statistically significant difference (P< 0.05) between the prevalence of typhoid fever and the occupation of the pregnant women examined. With respect to the location of the participants, subjects belonging to Semi-urban areas recorded the highest prevalence of 80.98%. There was statistically significant difference (P< 0.05) between the prevalence of typhoid fever and the location of the pregnant women examined. Pregnancy state makes the women more vulnerable to typhoid fever by affecting the physiology of pivotal organs, as such causing complications in pregnant women therefore early and prompt diagnosis of the infection is essential.
Economic Analysis of Agricultural Credit on Production Efficiency of Borrower Farms
Authors: Rani S. Padma
Published: February 2021

Credit is one of the most crucial but scarce inputs used in agriculture. Farm credit is an important instrument, which has been used to increase agricultural productivity. The main focus of this research is to examine the role of agricultural credits, production and efficiency of farms in Erode District of Tamil Nadu. Kavunthapadi and Modakurichi block of Erode district was selected. A complete enumeration of farm households which borrowed institutional crop loan in each of the sample villages was made. The survey was conducted among 60 borrowers and 45 non-borrowers farm households. In the present study, the efficiency of farms among borrower and non-borrower sample households was determined by the Stochastic Frontier production function of the Cobb- Douglas type had been used. And Tobit analysis was also done to know the effect of credit on farm efficiency. The efficiency scores obtained from first stage Stochastic Frontier Approach for borrower and non-borrower farms were used as dependent variable and a dummy variable to represent credit (X5i) were used as one of the independent variables in addition to other socio economic independent variables. Results of the model revealed that the number of borrower farms with a technical efficiency of more than 90 per cent were more (57 per cent of the total borrower farms) than that of non- borrower farms (33.3 per cent) which implies that the more percentage of farmers availed credit and adopted technology had higher technical efficiency level (90 per cent). The results also indicated that technical efficiency ranged from 0.41 to 0.99 for non borrowers and from 0.62 to 0.98 for borrowers. The results of Tobit regression analysis indicated that net operational area, farm experience, access to farm credit, had positive and significant relationship with the technical efficiency of the farmer.
Simulasi Perubahan Back Rake Angle Polycrystalline Diamond Carbide Drill Bit untuk Meminimalkan Keausan Pahat
Authors: Soegihardjo Oegik , Trinata Samuel
Published: February 2021

The drilling process of an oil well uses a drill bit to drill a hole to drain crude oil from the bowels of the earth to the ground. Tool wear occurs in every cutting or drilling process that uses tool bits. A drill bit is the general term for the tool blade used in the drilling process. Two types of tool bits that are commonly used are roller cone and Polycrystalline Diamond Carbide drill bit or PDC. The case being study is the wear out of the PDC drill bit, that causing unplanned bit trip. This research was conducted as an effort to reduce the wear that occurs on the PDC drill bit. The aim of the research is to simulate the changes of the back rake angle, so that the impact of the back rake angle's changes on the wear of the drill bit could be investigated. The results of the simulations were compared with the tool wear data that occurred at one of the oil drilling locations.
Synthesis of Polysubstituted Phenols by Rhodium‐Catalyzed C−H/Diazo Coupling and Tandem Annulation
Authors: Liu Min , Yan Kelu , Wen Jiangwei , Li Xue , Wang Xiaoyu , Lu Fengjie , Wang Xiu , Wang Hua
Published: February 2021

The rhodium(III)‐catalyzed C−H/diazo coupling and tandem annulation of 3‐oxopent‐4‐enenitriles have been proposed for the synthesis of polysubstituted phenols. Most products of phenols are obtained in good yields. Several preliminary mechanistic studies and derivatization reactions of phenol products were also performed. This method offers an alternative approach for the synthesis of useful diverse phenols.

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Weaning, parturitions and illnesses are recorded in rhesus macaque (Macaca mulatta) dental cementum microstructure
Authors: Cerrito Paola , Cerrito Leonardo , Hu Bin , Bailey Shara E. , Kalisher Rachel , Bromage Timothy G.
Published: February 2021

Many open questions in evolutionary studies relate to species' physiological adaptations, including the evolution of their life history and reproductive strategies. There are few empirical methods capable of detecting and timing physiologically impactful events such as weaning, parturition and illnesses from hard tissue remains of either extant or extinct species. Cementum is an incremental tissue with post eruption annual periodicity, which covers the tooth root and functions as a recording structure of an animal's physiology. Here we test the hypothesis that it is possible to detect and time physiologically impactful events through the analysis of dental cementum microstructure. Our sample comprises 41 permanent and deciduous teeth from male and female rhesus macaques (Macaca mulatta) with known medical, lifestyle and life history information. We develop a semi‐automated method of cementum histological analysis for the purpose of event detection and timing, aimed at significantly reducing the amount of intra‐ and interobserver errors typically associated with histological analyses. The results of our work show that we were able to detect known events including weaning, parturition, illness and physical trauma with high accuracy (false negative rate = 3.2%; n = 1), and to time them within an average absolute difference of 0.43 years (R2 = .98; p < .05). Nonetheless, we could not distinguish between the several types of stressful events underlying the changes in cementum microstructure. While this study is the first to identify a variety of life history events in macaque dental cementum, laying foundations for future work in conservation and evolutionary studies of both primates and toothed mammals at large, there are some limitations. Other types of analyses (possibly chemical ones) are necessary to tease apart the causes of the stressors.
An evaluation of the Early Learning Measure as a predictor of outcomes in early intensive behavioral intervention
Authors: Lewon Ainsley B. , Ghezzi Patrick M.
Published: February 2021

Research on early intensive behavioral intervention (EIBI) for young children diagnosed with autism spectrum disorder demonstrates that many children who receive EIBI achieve optimal outcomes posttreatment, while others benefit more modestly. Researchers are, therefore, increasingly interested in identifying the child‐related and treatment‐related variables that predict the full range of outcomes reported in the EIBI literature. The present study is a retrospective investigation into how early response to treatment as measured by the Early Learning Measure related to and predicted a child's clinical outcome at discharge. Results suggest that rapid mastery of responses in the vocal imitation and expressive labeling domains were predictive of higher levels of adaptive functioning, lower autism symptomology, and fewer required services and supports posttreatment. Early progress in these domains was a better predictor of a child's outcome than either pretreatment assessment scores or the child's age at intake.
REVERSE phenotyping—Can the phenotype following constitutive Tph2 gene inactivation in mice be transferred to children and adolescents with and without adhd?
Authors: Akhrif Atae , Roy Arunima , Peters Katharina , Lesch Klaus‐Peter , Romanos Marcel , Schmitt‐Böhrer Angelika , Neufang Susanne
Published: February 2021

Introduction

Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin‐synthesizing tryptophan hydroxylase‐2 (Tph2‐/‐) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD‐like model, we examined the Tph2‐/‐ phenotype in humans when considering allelic variation of TPH2 function (“reverse phenotyping”).

Methods

58 participants (6 females, 8–18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4‐choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G‐703T (rs4570625) polymorphism. To analyze the relation between TPH2 G‐703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators.

Results

We found that the relation between TPH2 G‐703T and aggression as part of the reverse Tph2‐/‐ phenotype was mediated by structure and function of the right middle and inferior frontal gyrus.

Conclusion

At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G‐703T‐dependent phenotype in humans. Additionally, we conclude that “reverse phenotyping” is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms.
Structural Insights into Malic Enzyme Variants Favoring an Unnatural Redox Cofactor
Authors: Liu Yuxue , Guo Xiaojia , Liu Wujun , Wang Junting , Kent Zhao Zongbao
Published: February 2021

The use of nicotinamide cytosine dinucleotide (NCD), a biocompatible nicotinamide adenosine dinucleotide (NAD) analogue, is of great scientific and biotechnological interest. Several redox enzymes have been devised to favor NCD, and have been successfully applied in creating NCD‐dependent redox systems. However, molecular interactions between cofactor and protein have still to be disclosed in order to guide further engineering efforts. Here we report the structural analysis of an NCD‐favoring malic enzyme (ME) variant derived from Escherichia coli. The X‐ray crystal structure data revealed that the residues located at position 346 and 401 in ME acted as the “gatekeepers” of the adenine moiety binding cavity. When Arg346 was substituted with either acidic or aromatic residues, the corresponding mutants showed substantially reduced NCD preference. Inspired by these observations, we generated Lactobacillus helveticus derived d‐lactate dehydrogenase variants at Ile177, the counterpart to Arg346 in ME, and found a similar trend in terms of cofactor preference changes. As many NAD‐dependent oxidoreductases share key structural features, our results provide guidance for protein engineering to obtain more NCD‐favoring variants.
Pivotal Role of Translation in Anti‐Infective Development
Authors: Friberg Lena E.
Published: February 2021

The value of model‐based translation in drug discovery and development is now effectively being recognized in many disease areas and among various stakeholders. Such quantitative approaches are expected to facilitate the selection on which compound to prioritize for successful development, predict the human efficacious dose based on preclinical data with adequate precision, guide design, and de‐risk later development stages. The importance of time‐dependencies, which are typically species‐dependent due to different turnover rates of biological processes, is, however, often neglected. For bacterial infections, the choice of dosing regimen is typically relying on preclinical pharmacokinetic (PK) and pharmacodynamic (PD) data, because the bacterial load and disease severity, and consequently the PK/PD relationship, cannot be quantified well on clinical data, given the low‐information end points used. It is time to recognize the limitations of using time‐collapsed approaches for translation (i.e., methods where targets are based on summary measures of exposure and response). Models describing the full time‐course captures important quantitative information of drug distribution, bacterial growth, antibiotic killing, and resistance development, and can account for species‐differences in the PK profiles driving the killing. Furthermore, with a model‐based approach for translation, we can take a holistic approach in development of a joint model for in vitro, in vivo, and clinical data, as well as incorporating information on the contribution of the immune system. Such advancements are anticipated to facilitate rational decision making during various stages of drug development and in the optimization of treatment regimens for different groups of patients.
Mapping mineralogy in evaporite basins through time using multispectral Landsat data: Examples from the Bonneville basin, Utah, USA
Authors: Radwin Mark H. , Bowen Brenda B.
Published: February 2021

The Bonneville basin, located in north‐western Utah, is a vast evaporite basin which is home to the world‐renowned Bonneville Salt Flats international speedway and is a highly valued landscape undergoing rapid change and anthropogenic influence. Air quality, snowpack, the local hydrological system, and state tourism are all impacted by the nature of the surface sediments exposed in the Bonneville basin. Mapping the Bonneville basin over time with remote sensing methods provides insight into the dynamics and impacts of the changing surface landscape. Utilizing the Landsat‐5 Thematic Mapper (TM) and Landsat‐8 Operational Land Imager (OLI) sensors, a set of band math indices are empirically established to map the predominant halite, gypsum, and carbonates mineralogical zones of the Bonneville basin. Spectral comparisons of representative samples from the study area and image‐derived spectra indicate the halite of the Bonneville basin is wet and that gypsum deposits are slightly mixed with halite. The established indices are assessed in four ways, all of which support the ability of the indices to accentuate the associated mineralogical endmembers. Two study areas within the Bonneville basin are investigated temporally from 1986, 1995, 2005, and 2016 and show changing patterns in mineral distribution that align with surface processes active through these timescales. These indices provide a resource for mapping mineralogy though time in evaporite basins globally with diverse applications for questions about land use and environmental change.
Effects of Phenanthrene Exposure on Cholesterol Homeostasis and Cardiotoxicity in Zebrafish Embryos
Authors: McGruer Victoria , Tanabe Philip , Vliet Sara M.F. , Dasgupta Subham , Qian Le , Volz David C. , Schlenk Daniel
Published: February 2021

Polycyclic aromatic hydrocarbons (PAHs) are pervasive pollutants in aquatic ecosystems, and developing fish embryos are especially sensitive to PAH exposure. Exposure to crude oil or phenanthrene (a reference PAH found in oil) produces an array of gross morphological abnormalities in developing fish embryos, including cardiotoxicity. Recently, studies utilizing transcriptomic analyses in several oil-exposed fish embryos found significant changes in the abundance of transcripts involved in cholesterol biosynthesis. Given the vital role of cholesterol availability in embryonic heart development, we hypothesized that cholesterol dysregulation in early development contributes to phenanthrene-induced cardiotoxicity. We exposed zebrafish embryos to 12 or 15 µM phenanthrene from 6 to 72 h post fertilization (hpf) and demonstrated that, in conjunction with pericardial edema and bradycardia, several genes (fdft1 and hmgcra) in the cholesterol biosynthetic pathway were significantly altered. When embryos were pretreated with a cholesterol solution from 6 to 24 hpf followed by exposure to phenanthrene from 24 to 48 hpf, the effects of phenanthrene on heart rate were partially mitigated. Despite changes in gene expression, whole-mount in situ staining of cholesterol was not significantly affected in embryos exposed to phenanthrene ranging in stage from 24 to 72 hpf. However, the 2-dimensional yolk area was significantly increased with phenanthrene exposure at 72 hpf, suggesting that lipid transport from the yolk to the developing embryo was impaired. Environ Toxicol Chem 2021;40:1586–1595. © 2021 SETAC
Development of a Sublethal Chronic Toxicity Test for the Northern Trout Gudgeon, Mogurnda mogurnda, and Application to Uranium, Magnesium, and Manganese
Authors: Pease Ceiwen J. , Trenfield Melanie A. , Mooney Thomas J. , van Dam Rick A. , Walker Samantha , Tanneberger Claudia , Harford Andrew J.
Published: February 2021

Many international guidance documents for deriving water quality guideline values recommend the use of chronic toxicity data. For the tropical fish northern trout gudgeon, Mogurnda mogurnda, 96-h acute and 28-d chronic toxicity tests have been developed, but both tests have drawbacks. The 96-h toxicity test is acute and has a lethal endpoint; hence it is not a preferred method for guideline value derivation. The 28-d method has a sublethal (growth) endpoint, but is highly resource intensive and is high risk in terms of not meeting quality control criteria. The present study aimed to determine the feasibility of a 7-d larval growth toxicity test as an alternative to the 96-h survival and 28-d growth tests. Once the method was successfully developed, derived toxicity estimates for uranium, magnesium, and manganese were compared with those for other endpoints and tests lengths within the literature. As a final validation of the 7-d method, the sensitivity of the 7-d growth endpoint was compared with those of 14-, 21-, and 28-d exposures. Fish growth rate, based on length, over 7 d was significantly more sensitive compared with existing acute toxicity endpoints for magnesium and manganese, and was similarly sensitive to existing chronic toxicity endpoints for uranium. For uranium, the sensitivity of the growth endpoint over the 4 exposure periods was similar, suggesting that 7 d as an exposure duration is sufficient to provide an indication of longer term chronic growth effects. The sensitivity of the 7-d method, across the 3 metals tested, highlights the benefit of utilizing the highly reliable short-term 7-d chronic toxicity test method in future toxicity testing using M. mogurnda. Environ Toxicol Chem 2021;40:1596–1605. © 2021 Commonwealth of Australia. Environmental Toxicology and Chemistry © 2021 SETAC.
Addressing data integration challenges to link ecological processes across scales
Authors: Zipkin Elise F , Zylstra Erin R , Wright Alexander D , Saunders Sarah P , Finley Andrew O , Dietze Michael C , Itter Malcolm S , Tingley Morgan W
Published: February 2021

Data integration is a statistical modeling approach that incorporates multiple data sources within a unified analytical framework. Macrosystems ecology – the study of ecological phenomena at broad scales, including interactions across scales – increasingly employs data integration techniques to expand the spatiotemporal scope of research and inferences, increase the precision of parameter estimates, and account for multiple sources of uncertainty in estimates of multiscale processes. We highlight four common analytical challenges to data integration in macrosystems ecology research: data scale mismatches, unbalanced data, sampling biases, and model development and assessment. We explain each problem, discuss current approaches to address the issue, and describe potential areas of research to overcome these hurdles. Use of data integration techniques has increased rapidly in recent years, and given the inferential value of such approaches, we expect continued development and wider application across ecological disciplines, especially in macrosystems ecology.
Consequences of the COVID‐19 pandemic on the postpartum course: Lessons learnt from a large‐scale comparative study in a teaching hospital
Authors: Kugelman Nir , Toledano‐Hacohen Mirit , Karmakar Debjyoti , Segev Yakir , Shalabna Eiman , Damti Amit , Kedar Reuven , Zilberlicht Ariel
Published: February 2021

Objective

To evaluate the consequences of COVID‐19 pandemic restrictions on the postpartum course.

Methods

A retrospective cross‐sectional study compared women who gave birth between March and April 2020 (first wave), between July to September 2020 (second wave), and a matched historical cohort throughout 2017–2019 (groups A, B, and C, respectively). Primary outcomes were postpartum length of stay (LOS), presentations to the emergency department (ED), and readmissions 30 days or longer after discharge. Following Bonferroni correction, p < 0.016 was considered statistically significant.

Results

In total, 3377 women were included: 640, 914, and 1823 in groups A, B, and C, respectively. LOS after birth (both vaginal and cesarean) was shorter in groups A and B compared to the control group (2.28 ± 1.01 and 2.25 ± 0.93 vs 2.55 ± 1.10 days, p < 0.001). Rates of ED presentations 30 days after discharge were higher in groups C and B compared to group A (6.63% and 6.45% vs 3.12%, p = 0.006). Rates of readmissions 30 days after discharge were 0.78%, 1.42%, and 1.09% (groups A, B, and C, respectively), demonstrating no statistical difference (p = 0.408).

Conclusion

During the COVID‐19 pandemic, there was a reduction or no change in rates of ED presentations and readmissions, despite the shortened LOS after delivery. A shift in policy regarding the postpartum LOS could be considered.
Surgical approaches to the superior mesenteric artery during minimally invasive pancreaticoduodenectomy: A systematic review
Authors: Nagakawa Yuichi , Watanabe Yusuke , Kozono Shingo , Boggi Ugo , Palanivelu Chinnusamy , Liu Rong , Wang Shin‐E , He Jin , Nishino Hitoe , Ohtsuka Takao , Ban Daisuke , Nakata Kohei , Endo Itraru , Tsuchida Akihiko , Nakamura Masafumi ,   Study group of Precision Anatomy for Minimally Invasive Hepato‐Biliary‐Pancreatic surgery (PAM‐HBP surgery)
Published: February 2021

Background

Minimally invasive pancreaticoduodenectomy (MIPD) has recently been safely performed by experts, and various methods for resection have been reported. This review summarizes the literature describing surgical approaches for MIPD.

Methods

A systematic literature search of PubMed (MEDLINE) was conducted for studies reporting robotic and laparoscopic pancreaticoduodenectomy; the reference lists of review articles were searched. Of 444 articles yielded, 23 manuscripts describing the surgical approach to dissect around the superior mesenteric artery (SMA), including hand‐searched articles, were assessed.

Results

Various approaches to dissect around the SMA have been reported. These approaches were categorized according to the direction toward the SMA when initiating dissection around the SMA: anterior approach (two articles), posterior approach (four articles), right approach (16 articles), and left approach (three articles). Thus, many reports used the right approach. Most articles provided a technical description. Some articles showed the advantage of their method in a comparison study. However, these were single‐center retrospective studies with a small sample size.

Conclusions

Various approaches for MIPD have been reported; however, few authors have reported the advantage of their methods compared to other methods. Further discussion is needed to clarify the appropriate surgical approach to the SMA during MIPD.