bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative Strategies for Enhancing Child Protection Practices in Pre-Primary Schools: A Case Study of Kira Municipality, Uganda
Authors:   Kyambogo University, Mutumba Safina , Samson Maani John , Busingye Sr. Evangelista
Published: August 2024

Child protection practices are measures and interventions intended to safeguard children against violence in school. These practices create safe environments that enable children to thrive. Some of these include the prevention of child abuse and neglect. Child protection agencies’ collaboration is a partnership that supports children’s well-being. This study investigated the contribution of child protection agencies’ collaboration on protection practices in Pre-primary schools in Kira Municipality, which has continued to be challenging. This study was informed by the social capital theory emphasizing the significance of social relationships, trust, and mutuality. The study used a descriptive cross-sectional survey design, and data was collected using quantitative and qualitative tools. These included document analysis checklists, interview guides, observation checklists, and questionnaires. The respondents included headteachers, Centre Management Committee members, parents, Local Council members, and Probation officers. The results indicated that schools rarely collaborated with child protection agencies to ensure that protection practices were implemented in pre-primary schools. In contrast, the probation officers reported that the schools didn’t involve them during the planning, though it was when they would know the areas for collaboration. Four significant recommendations for improving child protection practices are given. Child protection workers need to jointly develop plans that promote child safety and protection, train and build the capacity of educators on issues of child protection, increase resources and financial support to promote child safety and protection, and finally, advocate for laws and policies that promote children’s rights.
Higher Education Challenges Faced by Professors and Students After First Online Semester
Authors: BULAT Cristina Ionela
Published: August 2024

The study presents an analysis of the perceptions and experiences of both professors and students during the transition to online learning amid the COVID-19 pandemic. Key findings indicate a degree of consistency in the structure of online courses, with an emphasis on the importance of interaction between professors and students, highlighting the enduring significance of face-to-face contact in education. While course materials generally supported learning objectives, concerns regarding online assessment fairness and accuracy were noted. For students the preference for face-to-face courses was evident, but some expressed a preference for online learning. Digital communication platforms played a crucial role, with Zoom being widely adopted in the institution where the research was made. Professors faced higher workloads and technical challenges, while students adapted by dedicating more time to studying. Common consequences for students and professors included increased stress and workload, decreased teaching quality, and reduced interaction (among students and professor-students) with unique challenges for both groups. This study offers valuable insights for improving the online learning experience and highlights the importance of adaptability in the digital age.
Anti-tumor Effects of Triptonide Derived from Chinese Herb Tripterygium Wilfordii Hook F
Authors: Zhong Anthony
Published: August 2024

Tripterygium wilfordii Hook F (TwHF), a traditional Chinese herb, has been used to treat autoimmune and inflammatory diseases for centuries. In the past decades, anti-tumor effects of two key ingredients of TwHF, triptolide and celastrol, have been reported in numerous research studies and review articles. However, the importance of triptonide (another important ingredient of TwHF) in cancer therapy has not been recognized until recent years. In the article, we review recent advances of triptonide as an antitumor agent with a focus on its biological activities, action mechanisms and clinical development.
Dysregulated Ca2+ signaling, fluid secretion, and mitochondrial function in a mouse model of early Sjögren’s syndrome
Authors: Huang Kai-Ting , Wagner Larry E , Takano Takahiro , Lin Xiao-Xuan , Bagavant Harini , Deshmukh Umesh , Yule David I
Published: August 2024

Saliva is essential for oral health. The molecular mechanisms leading to physiological fluid secretion are largely established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sjögren’s syndrome (SS) are not fully understood. A major conundrum is the lack of association between the severity of inflammatory immune cell infiltration within the salivary glands and glandular hypofunction. In this study, we investigated in a mouse model system, mechanisms of glandular hypofunction caused by the activation of the stimulator of interferon genes (STING) pathway. Glandular hypofunction and SS-like disease were induced by treatment with 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA), a small molecule agonist of murine STING. Contrary to our expectations, despite a significant reduction in fluid secretion in DMXAA-treated mice,
in vivo
imaging demonstrated that neural stimulation resulted in greatly enhanced spatially averaged cytosolic Ca
2+
levels. Notably, however, the spatiotemporal characteristics of the Ca
2+
signals were altered to signals that propagated throughout the entire cytoplasm as opposed to largely apically confined Ca
2+
rises observed without treatment. Despite the augmented Ca
2+
signals, muscarinic stimulation resulted in reduced activation of TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca
2+
. However, super-resolution microscopy revealed a disruption in the intimate colocalization of Inositol 1,4,5-trisphosphate receptor Ca
2+
release channels in relation to TMEM16a. TMEM16a channel activation was also reduced when intracellular Ca
2+
buffering was increased. These data are consistent with altered local coupling between the channels contributing to the reduced activation of TMEM16a. Appropriate Ca
2+
signaling is also pivotal for mitochondrial morphology and bioenergetics and secretion is an energetically expensive process. Disrupted mitochondrial morphology, a depolarized mitochondrial membrane potential, and reduced oxygen consumption rate were observed in DMXAA-treated animals compared to control animals. We report that early in SS disease, dysregulated Ca
2+
signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction and likely the progression of SS disease.
Circular RNA HMGCS1 sponges miR-4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction
Authors: Zhang Ming , Du Guangyi , Xie Lianghua , Xu Yang , Chen Wei
Published: August 2024

Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of circHMGCS1 and miR-4521 were observed in diabetes-induced vascular endothelial dysfunction. The overexpression of circHMGCS1 or silencing of miR-4521 expedited the onset of diabetes and aggravated vascular endothelial dysfunction. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging miR-4521, leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of circHMGCS1 and miR-4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and miR-4521 could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.
Redistribution of fragmented mitochondria ensure symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes
Authors: Gekko Haruna , Nomura Ruri , Kuzuhara Daiki , Kaneyasu Masato , Koseki Genpei , Adhikari Deepak , Mio Yasuyuki , Carroll John , Kono Tomohiro , Funahashi Hiroaki , Wakai Takuya
Published: August 2024

In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without significant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Deletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2-cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca
2+
levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensure proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage.
Introducción a la Responsabilidad Relacional en el Contexto de Crisis Socio-ecológica
Authors: Amo-Grez Claudia
Published: August 2024

¿Qué hacer frente a la actual crisis socio-ecológica? Este artículo propone la noción de responsabilidad relacional como respuesta a esta pregunta, por tratarse de un principio ético idóneo para orientar la acción ante el tipo de situaciones implicadas en esta crisis; al mismo tiempo que brinda un marco analítico que enriquece las lecturas sobre las partes y fuerzas involucradas en dichas situaciones. Este artículo se vale de la integración y síntesis de reflexiones provenientes de múltiples disciplinas, tales como la filosofía, antropología, economía y psicología, para poner esta noción en contexto y mostrar su potencialidad. El cuerpo del artículo se divide en tres secciones. Las dos primeras tienen el propósito de situar la discusión en el contraste entre las dos formas de concebir el mundo que confluyen cuando la crisis socio-ecológica se aborda desde la responsabilidad relacional. Así, mientras la primera sección, examina los fundamentos ideológicos que alimentan esta crisis; la segunda, reflexiona sobre la relacionalidad, una forma alternativa de entender el mundo que, en el último tiempo, ha ido encontrando lugar en distintas disciplinas académicas. Luego, la tercera sección aborda la responsabilidad relacional en el contexto de la ética relacional y de las distintas formas en que se suele entender la responsabilidad. El artículo concluye con algunas notas finales sobre el valor de la responsabilidad relacional, en el contexto de la actual crisis socio-ecológica, así como de los desafíos que implica su adopción en la situación actual.
Psychological Profile of English Pedagogy Students: Attributional Styles, Academic Self-Concept and Self-Esteem
Authors: Vera Sagredo Angélica , Vega Pinochet Héctor
Published: August 2024

This article examines the relationship between attributional styles, academic self-concept and self-esteem in university students of English Pedagogy. Their profiles in these variables were identified by using a quantitative descriptive-correlational approach and a sample of 125 students. In order to fulfill the objective of the study, descriptive and comparative analyses were performed through T Student and ANOVA. Also, Pearson correlations were performed to identify the link between the dimensions of the instruments with respect to the sociodemographic variables. The results showed that students tend to attribute their failures to lack of effort, lack of ability and moderate academic self-efficacy. Females evidenced greater attribution of failure due to lack of ability and family conflicts. Correlations were found between several dimensions, highlighting the negative relationship between internal causes and lack of effort. These findings provide relevant information for future educational interventions in this population.
A Review of Present Advancement in Climate Smart Agriculture Techniques: Adaptation for Sustaining Crop Production under Climate Change
Authors: Kumari Niru , Pandey Amit Kumar , Singh Akhilesh Kumar , Singh Ashutosh
Published: August 2024

The growing global population is driving up demand for agricultural goods at a never-before-seen rate. Improving crop yield and quality is essential to meeting this growing demand. The yield and quality of agricultural crops may be greatly increased by using agronomic techniques. Although it is known that changing climate circumstances have a detrimental impact on crop development, yield, soil quality, and ultimately the nutritional content of agricultural food, such agronomic methods under changing climate conditions are insufficient to boost crop productivity. In order to increase the production potential of agricultural crops, several agronomic improvements have been made in the previous few decades. These include the application of resource conservation technology and conservation agricultural methods. Therefore, it is essential to adopt various adaptive agricultural practices that are specifically resource-conserving, such as crop diversification, mulching, crop rotation, agroforestry, intercropping, and the push-pull system of crop pest and disease management, etc. in order to effectively deal with such unfavourable situations. These agronomic approaches, which are being advocated to increase agricultural production and profitability, are described in the review along with their methods for enhancing crop performance and quality.
A Review on Toxic Effects of Pesticides on Physiological Aspects of Fish
Authors: Rana Inder Singh , Kumar Rajinder , Sharma Sushma
Published: August 2024

Pesticides are notorious for staying and spreading in the environment, and they can accumulate and disturb the food web, which endangers both animals and humans. This study summarizes the available information on the eco-toxicology of pesticides in fish. The majority of pesticides are released into the environment, and very few that are applied reach their biological goal; where they can accumulate and be hazardous to organisms that are not their intended targets. Their entry into aquatic ecosystems causes disastrous effects on flora and fauna. An attempt has been made to critically review the harmful effects of different pesticides on different fish species. This review will focus on the various alternations or changes in fish behavior (like as increased surface breathing, tremors in their fins, air gulping, irregular swimming and operculum movement), biochemical characteristics (such as antioxidant defense system damage caused by the production of ROS, altered levels of several oxidative stress indicators, including MDA, GST, SOD, CAT, GSH and GPx levels), blood parameters (like altered levels of RBC, WBC, MCH, MCV Hct and Hb contents) and histopathological changes (in liver, gills, intestine, kidney and gonads) caused by various pesticides. Higher concentrations of pesticides in the water bodies can lead to the mortality of fish species while sub-lethal concentrations have long-lasting effects.
Assessing Farmers' Vulnerability to Climate Change: Insights and Adaptive Strategies
Authors: M. H. Shankara , M. Shivamurthy , C. M. Savitha , A. S. Shashi Kiran , T.M Chaitra
Published: August 2024

Vulnerability of farmers to climate change is intimately related to poverty, as the poor are least able to respond to climatic stimuli. Further, certain regions of the world are more harshly affected by the effects of climate change than others. With this background the study was conducted to know the vulnerability of farmers to climate change and their suggestions to overcome its ill effects. The data was collected from the Central Dry Zone (Zone - IV) of Karnataka. Tiptur and Chiknayakanahalli taluks from Tumakuru district, Kadur from Chikmagalore district, Arsikere from Hassan district and Challakere from Chitradurga district were selected purposively for the study. Totally, the data was collected from 150 respondents. With respect to exposure of farmers to climate change, rainfall and temperature were selected and majority of farmers in the study area were severely exposed (0.822) and sensitive (0.894) to climate change with lower adaptive capacity (0.576) between the year 2013-2017. Climate Vulnerability Index (CVI) of Arsikere, Kadur, Tiptur, Chiknayakanahalli and Challakere taluk was 0.186, 0.226, 0.224, 0.220 and 0.241, respectively. The overall CVI value of all selected taluks of Central Dry Zone of Karnataka was 0.218. The data revealed that, the majority of the farmers suggested, Government has to take necessary steps to fill the water bodies in villages (I) followed by Providing more number of drip/ sprinkler irrigation facility to cover maximum farm families (II), Subsidies/compensation has to be given for the crops to make up the cost of cultivation due to weather aberrations (II), Development department should ensure supplying of production inputs at appropriate time in the villages (III), Support price has to be given to all the crop produce based on cost of cultivation (IV), Creating awareness to the farmers about appropriate adaptation measures against climate  change (V) etc.,
Evaluation of Human Energy Consumption in Paddy Cultivation Practices
Authors: Chaithanya Leela Krishna , Joshi Pratibha , Barua Sukanya , Shravani Kotha
Published: August 2024

As the majority of the framers are small and marginal in India accounts for almost 85%, the farming practices are usually doing manually. These manual practices demand much energy consumption from the farmers which ultimately results in the reduced efficiency, productivity of work. The objective of the study is to evaluate the Energy Expenditure Rate (EER), Cardiac Cost of Work (CCW), Cardiac Cost of Recovery (CCR), Total Cardiac Cost of Work (TCCW), and Physiological Cost of Work (PCW) in paddy cultivation practices. Sample size of 10 per activity was taken for the present study in the East and West Godavari districts of Andhra Pradesh. For all the components (EER, CCW, CCR, TCCW, and PCW), heart rate was taken at three different intervals viz. resting phase, working phase, and recovery phase. Each activity in the paddy cultivation was standardized to five minutes. Results found that EER was found to be very high (180.71%), (183.11%) in transplanting activity and threshing activity among female-dominated and male-dominated activities respectively. Similarly, CCW (245bpm, 240bpm); CCR (57.85bpm, 56.62bpm); TCCW (302.85bpm, 296.62bpm); PCW (60.57bpm, 59.32bpm) values were found high in the threshing activity which ranked first among male dominated activities and transplanting activity among female dominated activities. It can be concluded that farmers can opt the tools that are less energy-demanding. Such type of tools is drum seeder, improved sickle, Dapog method of paddy transplanting, etc. Extension agents can suggest the farmers about improved tools that are at low operational cost and can give maximum efficiency and productivity.
Evaluating the Impact of Mobile Disseminated Agricultural Services on Farmers' Attitudes in Dindigul District, Tamil Nadu, India
Authors: Priyanka R. , Sundaramari M.
Published: August 2024

Mobile phone plays a vital role to share the various information related to agricultural activities. The method of communication is very easy and understandable for the farming community and helps them to disseminate the information in timely manner and they directly keep in touch with the marketing agencies. Especially the mobile phone is used for to get aware about the marketing prices and weather forecast for agricultural operations. The research was conducted in Cuddalore district of Tamil Nadu. The respondents were 120 farmers selected by using the random sampling technique and collected information by using the interview schedule. The major findings of the study revealed that majority of the farmers 43.33 per cent had favourable attitude about agricultural services disseminated through mobile phone. And the relationship of profile characteristics with attitude revealed that out of ten characteristics, five characteristics namely - educational status, mass media exposure, extension agency contact economic motivation and Innovativeness were found to have positive and significantly correlated with the attitude of farmers towards the agricultural services disseminated through mobile phone.
Unlocking the Potential of Zero-tillage Farming: Challenges, Opportunities, and Key Influences on Adoption
Authors: Lakhani A. L. , Patel B. P. , Gajera M. N.
Published: August 2024

Zero tillage (ZT) is a crucial agricultural strategy that prioritizes little soil disturbance. This research investigates the future possibilities of ZT, concentrating on three critical dimensions: technology developments, climate change considerations, and possible rise in adoption rates. Precision agriculture, robotics, artificial intelligence, and biotechnology have been shown to play a critical role in improving ZT efficiency and sustainability. These advancements enable more intelligent and focused methods, lowering waste and harmonizing farming operations with overall sustainability goals. Climate change is also a crucial factor in influencing ZT's future. ZT's intrinsic qualities of soil moisture conservation, decreased erosion, and carbon sequestration make it an effective technique for climate mitigation and adaptation. According to the report, the worldwide need to address climate change may serve as a stimulus for ZT expansion, linking it with crucial agricultural initiatives in the future. The possible rise in ZT adoption rates is investigated in light of these technological and environmental aspects. The findings indicate that technology's role in eliminating obstacles and increasing efficiency, together with government and organizational backing, might encourage widespread ZT adoption, particularly in developing nations. Collaborative efforts among multiple stakeholders, including researchers, policymakers, farmers, and industry, are emphasized as critical to optimizing ZT for different situations and requirements. Zero Tillage's future possibilities are broad and varied, characterized by technical innovation, compatibility with climate goals, and a clear route to widespread implementation. The combination of these variables offers a favorable scenario for ZT, establishing it as a key technique in developing sustainable agriculture in the future. This study adds to our understanding of ZT's future trajectory and provides insights that can help direct its ongoing evolution and effect in the agriculture sector.
Mechanistic Insights and Genetic Approaches for Enhancing Submergence Tolerance in Rice
Authors: Bharti Arya , Kesari Ravi , Sinha Sweta , Nahakpam Sareeta , Kumar Mankesh , Roy Chandan
Published: August 2024

Rice, a pivotal staple crop, serves as a dietary foundation for approximately half of the global population. Its cultivation, traditionally reliant on submerged conditions, faces significant challenges due to sudden flooding events. The majority of rice varieties are highly sensitive to prolonged submersion beyond a mere seven days, resulting in substantial yield losses. As global climate patterns shift, the occurrence and intensity of flooding are predictable to increase, exacerbating this issue. Therefore, development of rice varieties having enhanced submergence tolerance is critical to sustaining productivity and ensuring food security in flood-prone regions. Understanding the physiological and biochemical mechanisms underlying submergence tolerance is crucial in this context. Key physiological mechanisms include the regulation of carbohydrate reserves for energy during low oxygen availability, ethylene-responsive factors, especially the Sub1A gene to, regulate growth and stress responses, curbing excessive elongation to conserve energy and enhance survival. Additionally, specialized tissues such as aerenchyma and adventitious roots improve oxygen transport and nutrient uptake under flooded conditions. Genetic approaches, including Marker-Assisted Selection (MAS), have been instrumental in the development of submergence-tolerant rice varieties. The integration of the Sub1 QTL, especially the Sub1A gene, into high-yielding rice varieties has led to significant advancements in breeding submergence-tolerant cultivars. These genetic improvements provide a promising solution to mitigate the detrimental effects of flooding on rice production, ensuring the stability and sustainability of this essential crop in the face of changing climate conditions. This review discusses various mechanisms adapted by rice and genetic advancements aimed at enhancing submergence tolerance in rice to secure food production for future generations.
Strain and rotation rate patterns of mainland Greece from continuous GPS data and comparison between seismic and geodetic moment release
Authors: Chousianitis Konstantinos , Ganas Athanassios , Evangelidis Christos P.
Published: April 2015

We processed data from ~100 continuous GPS stations to provide new insights into the crustal motion and deformation of central and western Greece. We used the derived velocity field to evaluate two‐dimensional strain and rotation rate tensors, and we mapped the dilatation and maximum shear strain rates. In central Peloponnese and Epirus, we documented a 90° switch in the extension direction, which can be explained on the basis of the plate boundary configuration. Evidence for an extended deformation pattern in central Greece was found. Additionally, we detected two pairs of shear belts, one in Akarnania‐NW Peloponnese and one in North Aegean. We delineated two rotational domains that dominate the present‐day pattern. Moreover, we saw no geodetic evidence for North Anatolian Fault growth toward central Greece. We translated the geodetic strain rates into rates of seismic moment release and compared them with earthquake catalog‐based moment rates. In the central Ionian Sea, the geodetic strain is completely released seismically, which is indicative of a fully coupled seismogenic zone. However, for most of the study area, the geodesy‐based moment rates are at least 2 times higher than the earthquake‐based rates. We attribute this mainly to earthquake catalog representativity over the long‐term situation. However, for the Gulf of Corinth, it is unrealistic to associate the high ratio of geodetic to seismic moment rates only to incompleteness of the earthquake catalog; instead, long‐term aseismic deformation must be an important mechanism accommodating a considerable portion of the strain budget, especially at its western part.
Investigating the recent apparent hiatus in surface temperature increases: 2. Comparison of model ensembles to observational estimates
Authors: Thorne Peter , Outten Stephen , Bethke Ingo , Seland Øyvind
Published: April 2015

To assess published hypotheses surrounding the recent slowdown in surface warming (hiatus), we compare five available global observational surface temperature estimates to two 30‐member ensembles from the Norwegian Earth System Model (NorESM). Model ensembles are initialized in 1980 from the transient historical runs and driven with forcings used in the CMIP5 experiments and updated forcings based upon current observational understanding, described in Part 1. The ensembles' surface temperature trends are statistically indistinguishable over 1998–2012 despite differences in the prescribed forcings. There is thus no evidence that forcing errors play a significant role in explaining the hiatus according to NorESM. The observations fall either toward the lower portion of the ensembles or, for some observational estimates and regions, outside. The exception is the Arctic where the observations fall toward the upper ensemble bounds. Observational data set choices can make a large difference to findings of consistency or otherwise. Those NorESM ensemble members that exhibit Nino3.4 Sea Surface Temperature (SST) trends similar to observed also exhibit comparable tropical and to some extent global mean trends, supporting a role for El Nino Southern Oscillation in explaining the hiatus. Several ensemble members capture the marked seasonality observed in Northern Hemisphere midlatitude trends, with cooling in the wintertime and warming in the remaining seasons. Overall, we find that we cannot falsify NorESM as being capable of explaining the observed hiatus behavior. Importantly, this is not equivalent to concluding NorESM could simultaneously capture all important facets of the hiatus. Similar experiments with further, distinct, Earth System Models are required to verify our findings.
Spatial variability of seasonal extreme precipitation in the western United States
Authors: Bracken C. , Rajagopalan B. , Alexander M. , Gangopadhyay S.
Published: April 2015

We examine the characteristics of 3 day total extreme precipitation in the western United States. Coherent seasonal spatial patterns of timing and magnitude are evident in the data, motivating a seasonally based analysis. Using a clustering method that is consistent with extreme value theory, we identify coherent regions for extremes that vary seasonally. Based on storm back trajectory analysis, we demonstrate unique moisture sources and dominant moisture pathways for each spatial region. In the winter the Pacific Ocean is the dominant moisture source across the west, but in other seasons the Gulf of Mexico, the Gulf of California, and the land surface over the midwestern U.S. play an important role. We find the El Niño–Southern Oscillation (ENSO) to not have a strong impact on dominant moisture delivery pathways or moisture sources. The frequency of extremes under ENSO is spatially coherent and seasonally dependent with certain regions tending to have more (less) frequent extreme events in El Niño (La Niña) conditions.
A novel missense mutation in the NSDHL gene identified in a Lithuanian family by targeted next‐generation sequencing causes CK syndrome
Authors: Preiksaitiene Egle , Caro Alfonso , Benušienė Eglė , Oltra Silvestre , Orellana Carmen , Morkūnienė Aušra , Roselló Mónica Pilar , Kasnauskiene Jurate , Monfort Sandra , Kučinskas Vaidutis , Mayo Sonia , Martinez Francisco
Published: April 2015

The NSDHL gene encodes 3β‐hydroxysteroid dehydrogenase involved in one of the later steps of the cholesterol biosynthetic pathway. Mutations in this gene can cause CHILD syndrome (OMIM 308050) and CK syndrome (OMIM 300831). CHILD syndrome is an X‐linked dominant, male lethal disorder caused by mutations in the NSDHL gene that result in the loss of the function of the NSDHL protein. CK syndrome is an allelic X‐linked recessive disorder. So far, 13 patients with CK syndrome from two families have been reported on. We present a new five‐generation family with affected males manifesting clinical features of CK syndrome. Next generation sequencing was targeted to a custom panel of 542 genes with known or putative implication on intellectual disability. Missense mutation p.Gly152Asp was identified in the NSDHL gene in the DNA sample of the affected male. Mutation carrier status was confirmed for all the obligate carriers in the family. The clinical features of the affected males in the family manifested as weak fetal movements, severe intellectual disability, seizures, spasticity, atrophy of optic discs, microcephaly, plagiocephaly, skeletal abnormalities, and minor facial anomalies, including a high nasal bridge, strabismus, and micrognathia. A highly significant preferential transmission of the mutation was observed in this and previous families segregating CK syndrome. Our report expands the clinical spectrum of this syndrome to include weak fetal movements, spasticity, and plagiocephaly, and transmission ratio distortion. The various findings in these patients increase our understanding of the diversity of the clinical presentation of cholesterol biosynthesis disorders. © 2015 Wiley Periodicals, Inc.
Delineation of the KIAA2022 mutation phenotype: Two patients with X‐linked intellectual disability and distinctive features
Authors: Kuroda Yukiko , Ohashi Ikuko , Naruto Takuya , Ida Kazumi , Enomoto Yumi , Saito Toshiyuki , Nagai Jun‐ichi , Wada Takahito , Kurosawa Kenji
Published: April 2015

Next‐generation sequencing has enabled the screening for a causative mutation in X‐linked intellectual disability (XLID). We identified KIAA2022 mutations in two unrelated male patients by targeted sequencing. We selected 13 Japanese male patients with severe intellectual disability (ID), including four sibling patients and nine sporadic patients. Two of thirteen had a KIAA2022 mutation. Patient 1 was a 3‐year‐old boy. He had severe ID with autistic behavior and hypotonia. Patient 2 was a 5‐year‐old boy. He also had severe ID with autistic behavior, hypotonia, central hypothyroidism, and steroid‐dependent nephrotic syndrome. Both patients revealed consistent distinctive features, including upswept hair, narrow forehead, downslanting eyebrows, wide palpebral fissures, long nose, hypoplastic alae nasi, open mouth, and large ears. De novo KIAA2022 mutations (p.Q705X in Patient 1, p.R322X in Patient 2) were detected by targeted sequencing and confirmed by Sanger sequencing. KIAA2022 mutations and alterations have been reported in only four families with nonsyndromic ID and epilepsy. KIAA2022 is highly expressed in the fetal and adult brain and plays a crucial role in neuronal development. These additional patients support the evidence that KIAA2022 is a causative gene for XLID. © 2015 Wiley Periodicals, Inc.
Early onset ectopia lentis due to a FBN1 mutation with non‐penetrance
Authors: Zhang Li , Lai Yu‐Hung , Capasso Jenina E. , Han Stella , Levin Alex V.
Published: April 2015

Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene. We report on a family with ectopia lentis. The propositus is a 6‐year‐old boy with bilateral superior‐temporal ectopia lentis. His echocardiogram was normal and he did not meet the revised Ghent criteria for Marfan syndrome. Molecular genetic testing revealed c.1948 C>T (p.Arg650Cys) in FBN1. The mother has visual acuity of 20/20 with −4.50 right eye and −2.50 left eye. She has no evidence of ectopia lentis. DNA analysis revealed that she has the same FBN1 mutation. Seven other maternal family members also have ectopia lentis. In conclusion, we report on a case of early‐onset autosomal dominant isolated ectopia lentis caused by FBN1 mutation that has previously been reported only in Marfan syndrome. The child's mother presumably represents a rare case of nonpenetrance. © 2015 Wiley Periodicals, Inc.
Spondyloepiphyseal dysplasia congenita caused by double heterozygous mutations in COL2A1
Authors: Kawano Osamu , Nakamura Akie , Morikawa Shuntaro , Uetake Kimiaki , Ishizu Katsura , Tajima Toshihiro
Published: April 2015

Spondyloepiphyseal dysplasia congenita (SEDC) is a group of rare inherited chondrodysplasias characterized by short stature, abnormal epiphyses, and flattened vertebral bodies. SEDC is usually caused by substitution of glycine residue with another amino acid in the triple helical domains of alpha 1 chains, which consist of type II collagen (COL2A1). Herein, we describe a unique case of SEDC with mild coxa vara (SEDC‐M) caused by double de novo COL2A1 mutations located on the same allele. One mutation, p.G504S, was previously described in patients with SEDC, whereas the other, p.G612A, was a novel mutation; both were located in the triple helical domain. Neither mutation was identified in the parents and appeared to be de novo. To the best of our knowledge, this is the first study involving a patient with a type II collagenopathy with two COL2A1 mutations on the same allele. The case was characterized by a more severe phenotype compared with previously reported cases involving a single p.G504S mutation, which may have been the result of the double mutation. © 2015 Wiley Periodicals, Inc.
Mosaic tetrasomy 20p associated with osteoporosis and recurrent fractures
Authors: Maziad Asmaa S. Abu , Seaver Laurie H.
Published: April 2015

Tetrasomy 20p is a very rare chromosome abnormality, with only two single cases previously reported in the literature, both fetuses with multiple congenital anomalies, osteopenia, and fractures. We report on the first case of mosaic tetrasomy 20p in a 13‐year‐old male. Amniocentesis karyotype showed mosaicism (73% of cells) for a supernumerary marker chromosome, an isodicentric chromosome 20p. At birth, cord blood karyotype was normal in all cells but uroepithelial cells showed the marker chromosome in 30% of cells analyzed. Chromosomal single nucleotide polymorphism (SNP) microarray using buccal cells confirmed the previous result with mosaicism estimated at 59% of cells. His course has been complicated by profound osteoporosis with recurrent nontraumatic fractures and vertebral compression leading to significant disability. This report describes the phenotype and evaluation of mosaic pure tetrasomy 20p syndrome and compares to nonmosaic tetrasomy 20p and trisomy 20p syndromes, both of which have been previously reported in association with osteopenia and fractures. The pathophysiology of osteoporosis in tetrasomy 20p is unknown. We hypothesize that overexpression of bone morphogenetic protein 2 may be the underlying mechanism of osteoporosis and recurrent fractures. © 2015 Wiley Periodicals, Inc.
Delineation of the clinically recognizable 17q22 contiguous gene deletion syndrome in a patient carrying the smallest microdeletion known to date
Authors: Martínez‐Fernández María Luisa , Fernández‐Toral Joaquin , Llano‐Rivas Isabel , Bermejo‐Sánchez Eva , MacDonald Alexandra , Martínez‐Frías María Luisa
Published: April 2015

We describe a patient with a 1.34 Mb microdeletion at chromosome band 17q22, which is also present in his affected mother. To better delineate this microdeletion syndrome, we compare the clinical and molecular characteristics of 10 previously reported cases and our patient. Of these, the present patient has the smallest deletion which includes five genes: MMD, TMEM100, PCTP, ANKFN1, and NOG. We compare the clinical manifestations described in relation to NOG, since this is the only gene whose loss is shared by our patient and the other eight patients. Previously, the clinical patterns associated with NOG mutations have been included under the general term “NOG‐related symphalangism spectrum disorder (NOG‐SSD).” Based on our analyses, and considering that there is a clinical correlation observed in cases with a “17q22 microdeletion including NOG” of which the main characteristics can be contributed to loss of this gene, we propose that the clinical patterns observed in these patients should be named as NOG‐spectrum disorder‐contiguous gene syndrome (NOGSD‐CGS). This designation is important for clinicians because when a patient has defects concordant with alterations of NOG but also presents other anomalies not related to this gene, they would be able to suspect the existence of a microdeletion affecting 17q22, therefore, allowing an early diagnosis. This will also enable the clinician to provide the family with adequate information about the prognosis and the risk of reoccurrence in future potential offspring. © 2015 Wiley Periodicals, Inc.
Good teaching is good teaching: A narrative review for effective medical educators
Authors: Berman Anthony C.
Published: April 2015

Educators have tried for many years to define teaching and effective teachers. More specifically, medical educators have tried to define what characteristics are common to successful teachers in the healthcare arena. The goal of teacher educators has long been to determine what makes an effective teacher so that they could do a better job of preparing future teachers to have a positive impact on the learning of their students. Medical educators have explored what makes some of their colleagues more able than others to facilitate the development of healthcare professionals who can successfully and safely meet the needs of future patients. Although there has historically been disagreement regarding the characteristics that need be developed in order for teachers to be effective, educational theorists have consistently agreed that becoming an effective teacher is a complex task. Such discussions have been central to deciding what education at any level is really all about. By exploring the literature and reflecting upon the personal experiences encountered in his lengthy career as a teacher, and as a teacher of teachers, the author reaches the conclusions that teaching is both art and science, that “good teaching is good teaching” regardless of the learning environment or the subject to be explored, and that the characteristics making up an effective medical educator are really not much different than those making up effective educators in any other area. Anat Sci Educ 8: 386–394. © 2015 American Association of Anatomists.
High fat diet‐Induced obesity alters vitamin D metabolizing enzyme expression in mice
Authors: Park Jeong Min , Park Chan Yoon , Han Sung Nim
Published: April 2015

Low serum 25(OH)D concentrations have been reported in obese humans. Inadequate sun exposure and impaired hepatic 25‐hydroxylation have been suggested as possible reasons for obesity‐associated vitamin D deficiency; however, the underlying mechanism has not been elucidated. We investigated the effects of high fat diet‐induced obesity on vitamin D status and vitamin D metabolizing enzyme expression. Male C57BL mice (4 weeks old) were fed control diet containing 10% energy from fat (control group) or high fat diet containing 45% energy from fat (obese group) for 18 weeks. There were no differences in serum 25(OH)D concentrations between two groups, while serum 1,25(OH)2D concentrations were significantly higher in obese mice. Hepatic mRNA levels of 25‐hydroxylases (Cyp2r1, Cyp27a1, and Cyp2j3) were lower in the obese group (31, 30, and 48% lower, respectively). Renal 1α‐hydroxylase (Cyp27b1) mRNA levels were higher and 24‐hydroxylase (Cyp24) mRNA levels were lower in the obese group. Serum 1,25(OH)2D concentrations correlated positively with renal Cyp27b1 expression levels and negatively with renal Cyp24 expression levels. Serum PTH concentrations were higher in obese mice. In visceral adipose tissue, Cyp27a1, Cyp2j3, and vitamin D receptor mRNA levels were higher in obese mice. Overall, vitamin D metabolizing enzyme expression was influenced by high fat diet‐induced obesity, which might partly explain the mechanisms of the altered vitamin D endocrine system associated with obesity. Higher serum PTH and 1,25(OH)2D concentrations in obese mice suggest abnormal regulation of serum 1,25(OH)2D concentrations due to hyperparathyroidism, which might have contributed to lower hepatic 25‐hydroxylase mRNA levels. © 2015 BioFactors, 41(3):175–182, 2015
Designing cell lines for viral vaccine production: Where do we stand?
Authors: Genzel Yvonne
Published: April 2015

Established animal cells, such as Vero, Madin Darby canine kidney (MDCK) or chicken embryo fibroblasts (CEFs), are still the main cell lines used for viral vaccine production, although new “designer cells” have been available for some years. These designer cell lines were specifically developed as a cell substrate for one application and are well characterized. Later screening for other possible applications widened the product range. These cells grow in suspension in chemically defined media under controlled conditions and can be used for up to 100 passages. Scale‐up is easier and current process options allow cultivation in disposable bioreactors at cell concentrations higher than 1×107 cells/mL. This review covers the limitations of established cell lines and discusses the requirements and screening options for new host cells. Currently available designer cells for viral vaccine production (PER.C6, CAP, AGE1.CR, EB66 cells), together with other new cell lines (PBS‐1, QOR/2E11, SogE, MFF‐8C1 cells) that were recently described as possible cell substrates are presented. Using current process knowledge and cell line development tools, future upstream processing could resemble today's Chinese hamster ovary (CHO) cell processes for monoclonal antibody production: small scale bioreactors (disposable) in perfusion or fed‐batch mode with cell concentrations above 1×108 cells/mL.
Identification of ribonucleotide reductase mutation causing temperature‐sensitivity of herpes simplex virus isolates from whitlow by deep sequencing
Authors: Daikoku Tohru , Oyama Yukari , Yajima Misako , Sekizuka Tsuyoshi , Kuroda Makoto , Shimada Yuka , Takehara Kazuhiko , Miwa Naoko , Okuda Tomoko , Sata Tetsutaro , Shiraki Kimiyasu
Published: April 2015

Key Clinical Message

Herpes simplex virus 2 caused a genital ulcer, and a secondary herpetic whitlow appeared during acyclovir therapy. The secondary and recurrent whitlow isolates were acyclovir‐resistant and temperature‐sensitive in contrast to a genital isolate. We identified the ribonucleotide reductase mutation responsible for temperature‐sensitivity by deep‐sequencing analysis.