bluuebunny/crossref_metadata_2025 huggingface dataset:
ЯКІСТЬ ПРОДУКЦІЇ ЯК ІСТОТНА УМОВА ГОСПОДАРСЬКОГО ДОГОВОРУ ПОСТАВКИ
Authors: Мамченко Ю. А.
Published: July 2021

Актуальність статті полягає в тому, що однією з умов договору, яка характеризує предмет купівлі-продажу з точки зору придатності його до використання за цільовим призначенням, є умова щодо якості продукції. Якість продукції – це сукупність властивостей і характеристик, які відображають рівень новизни, надійність, довговічність, економічність продукції (товарів) і зумовлюють її здатність задовольнити відповідно до свого призначення потреби споживачів. Якість речей, що продаються, повинна відповідати стандарту, технічним регламентам або зразкам, встановленим для речей такого роду. Вимоги до певних видів товарів встановлюються нормативними актами зі стандартизації: національними стандартами України, галузевими стандартами, технічними регламентами тощо. З метою запобігання реалізації продукції, небезпечної для життя, здоров’я та майна громадян і навколишнього середовища, сприяння споживачеві у компетентному виборі продукції проводиться обов’язкова (щодо окремих видів товарів) або добровільна сертифікація. Якщо у договорі відсутні умови про якість проданої речі, то вона за якістю повинна відповідати вимогам, що звичайно пред’являються, тобто бути придатною для звичайного використання за своїм призначенням або для цілей, передбачених договором. Наголошено, що визначення якості товару за стандартом припускає, що якість товару, що поставляється, точно відповідає визначеному стандарту – документу, розробленого на основі консенсусу та затверджений уповноваженим органом, що встановлює призначені для загального і багаторазового використання правила, інструкції або характеристики, які стосуються діяльності чи її результатів, включаючи продукцію, процеси або послуги, дотримання яких є необов’язковим. Стандарт може містити вимоги до термінології, позначок, пакування, маркування чи етикетування, які застосовуються до певної продукції, процесу чи послуги. Зроблено висновок, що різниця між гарантійним строком і строком придатності полягає в тому, що якщо зі спливом гарантійного терміну товар може не втратити своїх властивостей і може використовуватися в майбутньому впродовж невизначеного часу, то зі спливом терміну придатності товар, як правило, втрачає свої властивості, що робить неможливим його використання за призначенням. Окрім того, при виявленні в товарі недоліків у період дії гарантійного терміну можливе їх усунення шляхом ремонту, однак, як правило, неможливе виправлення недоліків, які виявилися у товарах після спливу терміну придатності.
ВІДОМЧИЙ КОНТРОЛЬ В СИСТЕМІ ГАРАНТІЙ ПРАВ ОСОБИ ПІД ЧАС ПРОВЕДЕННЯ СЛІДЧИХ (РОЗШУКОВИХ) ДІЙ
Authors: Конюшенко Я. Ю.
Published: July 2021

В статті визначено доктринальні підходи до поняття «забезпечення прав і свобод людини». Встановлено, що сфера кримінального провадження є такою, в якій найбільш звужуються та можуть бути порушені конституційні права і свободи особи, оскільки діяльність органів досудового розслідування пов’язана із застосуванням обмежень прав людини та у визначених випадках. Виходячи з цього, запропоновано визначати забезпечення прав і свобод людини в сфері кримінального провадження як діяльність уповноважених органів (органи досудового розслідування, прокуратура, суд), спрямовану на недопущення порушень прав і свобод кожного учасника кримінального провадження, контроль за додержанням прав людини та захист порушених прав. Щодо визначення гарантій прав учасників кримінального провадження під час проведення слідчих (розшукових) дій, автор дійшов висновку про те, що вони є складовою частиною гарантій кримінального провадження в цілому. Такі гарантії спрямовані на забезпечення виконання завдань кримінального провадження, реалізацію його засад, додержання належної правової процедури та недопущення порушень прав і свобод учасників слідчої (розшукової) дії та в необхідних випадках сприяють відновленню порушених прав учасників кримінального провадження. Розглянуто відомчий контроль за проведенням слідчих (розшукових) дій як одну з основних гарантій забезпечення прав, свобод та законних інтересів особи. Запропоновано визначати відомчий контроль як управлінську функцію керівників органів дізнання або досудового розслідування з метою виконання завдань кримінального провадження, додержання прав і свобод учасників дізнання та досудового розслідування, визначення законності дій слідчого або дізнавача, а також недоліків у здійсненні досудового розслідування з метою якнайшвидшого їх усунення. Окреслено ряд проблемних питань під час здійснення відомчого контролю за проведенням дізнавачем та слідчим слідчих (розшукових) дій, зокрема, щодо надання вказівок, витребування матеріалів кримінального провадження керівником органу дізнання або досудового розслідування вищого рівня, співвідношення повноважень слідчого та керівника органу досудового розслідування. На підставі проведеного дослідження запропоновано внесення змін до Кримінального процесуального кодексу України.
ОБСТАВИНИ, ЩО ПІДЛЯГАЮТЬ ДОКАЗУВАННЮ НА ПОЧАТКОВОМУ ЕТАПІ РОЗСЛІДУВАННЯ КРИМІНАЛЬНИХ ПРАВОПОРУШЕНЬ, ПОВ’ЯЗАНИХ ІЗ ЗАЙНЯТТЯМ ГРАЛЬНИМ БІЗНЕСОМ
Authors: Пиняга Р. О.
Published: July 2021

У статті деталізовано предмет доказування з урахуванням криміналістичної характеристики кримінальних правопорушень, пов’язаних із зайняттям гральним бізнесом. Визначено, що до події кримі- нального правопорушення належать насамперед технологія та спосіб за- йняття гральним бізнесом, час і місце його вчинення. Встановлення винува- тості обвинуваченого, форми вини, мотиву й мети вчинення кримінального правопорушення має на меті визначення кількості осіб, причетних до кри- мінального правопорушення, характеру розподілу ролей між ними, даних про фігурантів (вік, осудність, ознаки зовнішності, професійні навички), інших ознак, що характеризують ту чи іншу форму співучасті (кількість співучасників, стійкість, попередня змова чи зорганізованість, мета ді- яльності, наявність плану). Також необхідно встановити спосіб легаліза- ції доходів, одержаних злочинним шляхом. З’ясовано, що для розслідування злочинів, пов’язаних із зайняттям гральним бізнесом, важливе значення має розроблення обставин, що підлягають доказуванню. Зазначені обставини тісно пов’язані з предметом доказування. У науковій літературі останню категорію визначають по-різному: як систему (сукупність) фактів й обставин об’єктивної дійсності, що мають матеріально-правове (кримінальне й цивільне) та процесуальне (кримінальне й цивільне) значення і які є необхідною й достатньою фактичною підставою для вирішення кримінальних справ остаточно і по суті. Зроблено висновок, що предмет доказування у кримінальних провадженнях щодо злочинів, пов’язаних із зайняттям гральним бізнесом, деталізовано з урахуванням особливостей криміналістичної характеристики цієї категорії кримі- нальних правопорушень. На встановлення події злочину впливають: технологія, спосіб та місце зайняття гральним бізнесом, використане обладнання, категорії гравців. Винуватість обвинуваченого залежить від функції, яку він виконує у злочинній групі, виду та форми співучасті. Потребує встановлення розмір матеріальної шкоди, завданої гравцям в азартні ігри, а також напрями легалізації (відмивання) доходів, одержаних злочинним шляхом. Запропоновано поширити відповідальність за зайняття гральним бізнесом на всі категорії суб’єктів, які організовують та проводять азартні ігри з метою одержання прибутку, з унесенням відповідних змін і доповнень до Закону України «Про заборону грального бізнесу в Україні».
El género Onthophagus Latreille, 1802 (Coleoptera: Scarabaeidae) de México
Authors:   Instituto de Ecología A.C., Moctezuma Victor
Published: July 2021

Se utilizó información proveniente de literatura para compilar el listado de la fauna de Onthophagus de México. Se encontraron un total de 120 especies, de las cuales 85 son endémicas de México. Se incluyen los patrones de distribución originalmente propuestos porHalffter (1964) y comentarios adicionales para la mayoría de las especies. Se encontraron registros de especies para todos los estados de la República Mexicana, con excepción de Baja California. México es el centro de diversificación de Onthophagus de América, con aproximadamente el 62% de las especies descritas para el continente. Oaxaca es el estado con mayor riqueza de especies y mayor número de endemismos. Se discuten los factores que promovieron la diversificación de Onthophagus en México. Onthophagus mesoamericanusZunino y Halffter, 1988 es resucitado de la sinonimia previa.
Leapfrogging in Marketing: Empirical Analysis of Kenyan Mobile Phone Industry
Authors: Chepkoech Mae , Lagat Charles , L. Frankwick Gary
Published: July 2021

Purpose: This paper aims to analyze the concept of leapfrogging in the mobile phone industry in the Republic of Kenya.
Design/Methodology: The study adopted a cross-sectional research design, stratified and simple random sampling techniques in collecting data from 349 respondents picked from a population of 15506 employees of three Cosmopolitan County Governments in Kenya.
Findings: Outcome indicates that; perceived product quality and perceived switching cost positively and significantly influence intentions to Leapfrog. However, the urgency to replace does not influence choices to leapfrog.
Originality/value: The study findings bring a new understanding of the determinants of consumer leapfrogging and their intentions to leapfrog in the mobile phone industry and highlight the role perceived product quality and switching cost play in determining intention leapfrog.
Rank Approach for Equality Relations of BLUPs in Linear Mixed Model and its Transformed Model
Authors: ERİŞ BÜYÜKKAYA Melek , GÜLER Nesrin , YİĞİT Melike
Published: July 2021

A linear mixed model ($\LMM$) $\M :\yy = \mxX\BETA + \mxZ\uu + \EPS $ with general assumptions and its transformed model $\T:\mxT\yy = \mxT\mxX\BETA + \mxT\mxZ\uu + \mxT\EPS $ are considered. This work concerns the comparison problem of predictors under $\M$ and $\T$. Our aim is to establish equality relations between the best linear unbiased predictors ($\BLUP$s) of unknown vectors under two $\LMM$s $\M$ and $\T$ through their covariance matrices by using various rank formulas of block matrices and elementary matrix operations.
Prevalência de ortorexia nervosa em graduandos universitários da área de saúde: Uma revisão descritiva
Authors: Brandão Vitor Coêlho Silva , Xavier Wanessa de Souza , Ambrósio Carmem Lygia Burgos , Santana Raquel Araújo de
Published: July 2021

A expressão Ortorexia Nervosa (ON) está relacionada à “orthos” sendo indicativo de correto e “o-rexis” de apetite, sendo definida como uma obsessão por alimentação saudável. O público mais acometido é o de adolescente e adultos jovens do sexo feminino, e apresenta como consequência diversos prejuízos sociais e psicológicos. O objetivo do estudo foi descrever a prevalência de comportamentos com tendência a ON em graduandos universitários da área de saúde através de uma revisão descritiva. A pesquisa realizou-se nas bases PubMed, Scielo e Bireme por meio dos termos combinados (ortorexia nervosa) AND (graduandos universitários) OR (comportamento alimentar); (transtorno alimentar) AND (graduandos universitários) OR (comportamento alimentar); bem como seus respectivos termos em inglês. A busca resultou em 119 publicações e após a triagem, 11 estudos foram selecionados. Em relação às publicações foram extraídos os seguintes dados: título do estudo, ano de publicação, autores, objetivo, amostra e principais resultados. A maioria dos estudos selecionados abordou alunos do curso de Nutrição, porquanto acredita-se que eles constituem um grupo de risco em virtude do conhecimento sobre alimentação saudável, característica não observada em outro subgrupo populacional, e utilizou o questionário ORTO-15 para levantamento dos dados sobre alimentação. O percentual médio da presença de comportamentos de risco para ON foi aproximadamente 85,31%. Os resultados demonstraram uma maior prevalência de comportamentos de risco entre mulheres. Observou-se, portanto, que os estudantes apresentaram elevada frequência de comportamentos de risco para o desenvolvimento da ON, tornando os mesmos suscetíveis as consequências sociais, psicológicas e de saúde motivadas por esse distúrbio.
Sampling nesting sea turtles: optimizing survey design to minimize error
Authors: Whiting AU , Chaloupka M , Pilcher N , Basintal P , Limpus CJ
Published: July 2021

Many sea turtle studies globally use counts of nesting activities as a proxy for population abundance estimates and as an indicator of trends within the population. Often these populations are sampled temporally and spatially, but few previous studies have examined the impact of different sampling techniques on the accuracy of these estimates. We investigated temporal sampling errors using a multi-species approach, examining 10 populations comprising green, loggerhead and leatherback sea turtles. Sampling errors were investigated from random, regular and continuous sampling regimes spanning 5-80% coverage. A count approach was used rather than an individual-based capture-mark-recapture approach to broaden the scope and application of the research. Modelling showed that even low survey coverage of 5% gave reasonably accurate estimates of annual nesting activity, with estimated errors of ca. 20% (mean + 1 SD equalling 84.1% of surveys). Survey error is low relative to changes in abundance from the inter-annual variations in nesting activity that occur in sea turtle populations. Thus, annual studies are important to estimate sea turtle abundance, even if these studies have low survey coverage. An increase in survey effort may be more cost effective if spent combining estimates of total nesting activity with sampling turtles as part of a capture-mark-recapture study. This approach will provide a second estimate of annual abundance as well as an estimate of demographic parameters including clutch frequencies, remigration intervals, survivorship, immigration and emigration. This estimation of sampling errors may be useful in the design of monitoring programmes and can be used to guide management and policy decisions.
First finding of the family Rhynchomolgidae (Copepoda: Cyclopoida) in the Gulf of Mexico, with the description of a new species
Authors: Varela Carlos , Price W. Wayne , Middlebrooks Michael L. , Ambrosio Louis J.
Published: July 2021

The genus Critomolgus Humes and Stock, 1983 represents a group of 34 species of copepods associated with marine invertebrates. Most of these species have been collected in associations with species of the phyla Cnidaria and Echinodermata in several localities in the Indian, Pacific and Atlantic Oceans with three species reported in the Mediterranean Sea. This is the first occasion in which a species belonging to the genus Critomolgus and the family Rhynchomolgidae Humes and Stock, 1972 is recorded for the Gulf of Mexico. Here, we describe a new species of marine copepod, Critomolgus walteri Varela, Price, Middlebrooks et Ambrosio, associated with the octocorals Leptogorgia virgulata (Lamarck, 1815) and L. hebes Verrill, 1869 in 3.3 meters of water in Tampa Bay, Florida. This species possesses characters that unite it with other members of the genus; however, it differs from all other species due to the body length and unique leg 5 and maxilla l characters. This new species provides evidence that much diversity remains to be discovered in the waters of the Gulf of Mexico and future sampling efforts should target this region.
Elevational gradients do not affect thermal tolerance at local scale in populations of livebearing fishes of the genus Limia (Cyprinodontiformes: Poeciliinae)
Authors: Rodriguez-Silva Rodet , Schlupp Ingo
Published: July 2021

One of the main assumptions of Janzen’s mountain passes hypothesis is that due the low overlap in temperature regimes between low and high elevations in the tropics, organisms living in high-altitude evolve narrow tolerance for colder temperatures while low-altitude species develop narrow tolerance for warmer temperatures. Some studies have questioned the generality of the assumptions and predictions of this hypothesis suggesting that other factors different to temperature gradients between low and high elevations may explain altitudinal distribution of species in the tropics. In this study we test some predictions of the Janzen’s hypothesis at local scales through the analysis of the individual thermal niche breadth in populations of livebearing fishes of the genus Limia and its relationship with their altitudinal distribution in some islands of the Greater Antilles. We assessed variation in tolerance to extreme temperatures (measured as critical thermal minimum (CTmin) and maximum (CTmax) and compared thermal breadth for populations of eight species of Limia occurring in three Caribbean islands and that occupy different altitudinal distribution. Our results showed that species analyzed had significant differences in thermal limits and ranges. Generally, species distributed in high and low elevations did not differ in thermal limits and showed a wider range of thermal tolerance. However, species living in mid-elevations had narrower range of temperature tolerance. We found no significant effect of phylogeny on CTmin, CTmax and thermal ranges among species. This study did not provide evidence supporting Janzen’s hypothesis at a local scale since thermal tolerance and altitudinal distribution of Limia species were not related to temperature gradients expected in nature. Phylogeny also did not explain the patterns we observed. We suggest that biotic factors such as species interactions, diet specializations, and others should be considered when interpreting current distribution patterns of Limia species.
Production of D-Allose From D-Allulose Using Commercial Immobilized Glucose Isomerase
Authors: Choi Mi Na , Shin Kyung-Chul , Kim Dae Wook , Kim Baek-Joong , Park Chang-Su , Yeom Soo-Jin , Kim Yeong-Su
Published: July 2021

Rare sugars are regarded as functional biological materials due to their potential applications as low-calorie sweeteners, antioxidants, nucleoside analogs, and immunosuppressants. D-Allose is a rare sugar that has attracted substantial attention in recent years, owing to its pharmaceutical activities, but it is still not widely available. To address this limitation, we continuously produced D-allose from D-allulose using a packed bed reactor with commercial glucose isomerase (Sweetzyme IT). The optimal conditions for D-allose production were determined to be pH 8.0 and 60°C, with 500 g/L D-allulose as a substrate at a dilution rate of 0.24/h. Using these optimum conditions, the commercial glucose isomerase produced an average of 150 g/L D-allose over 20 days, with a productivity of 36 g/L/h and a conversion yield of 30%. This is the first report of the successful continuous production of D-allose from D-allulose by commercial glucose isomerase using a packed bed reactor, which can potentially provide a continuous production system for industrial applications of D-allose.
Empowered by Intertwined Theory and Practice – Experiences From a Diabetes Sports Camp for Physically Active Adults With Type 1 Diabetes
Authors: Mattsson Stig , Adolfsson Peter , Jendle Johan , Bengtsson Viktor , Sparud-Lundin Carina
Published: July 2021

Aims

To describe the experiences of individuals with diabetes type 1 (T1D) participating in diabetes sports camps and how acquired knowledge could be used in daily self-management.

Methods

Semi-structured telephone interviews were conducted with 15 adults with T1D. A strategic sample procedure was chosen. The interviews were analyzed using qualitative content analysis.

Results

The overarching theme ”Empowered by intertwined theory and practice”, included three main categories: Learning in a motivation-enhancing environment, incorporation of new habits and perceptions of glycemic control and health-related outcomes. The participants considered the camp to be an excellent opportunity to share feelings, ideas, and knowledge. They felt empowered by the camp atmosphere as well as supportive environment. After the camp, the general well-being was improved by incorporating new habits and improvements in glucose control.

Conclusions

A diabetes sports camp constitutes an excellent, but resource-intensive, complimentary support in diabetes care and provides opportunities for T1D individuals to become more independent and autonomous. The findings indicate the need for more directed learning activities for individuals with type 1 diabetes and health care providers to increase their competence in the area of T1D and exercise in order to adequately manage counseling in various types of sports.
Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain
Authors: Abbas Eman , Hassan Mohamed A. , Sokpor Godwin , Kiszka Kamila , Pham Linh , Kerimoglu Cemil , Fischer Andre , Nguyen Huu Phuc , Staiger Jochen F. , Tuoc Tran
Published: July 2021

Oligodendrocytes are responsible for axon myelination in the brain and spinal cord. Generation of oligodendrocytes entails highly regulated multistage neurodevelopmental events, including proliferation, differentiation and maturation. The chromatin remodeling BAF (mSWI/SNF) complex is a notable regulator of neural development. In our previous studies, we determined the indispensability of the BAF complex scaffolding subunits BAF155 and BAF170 for neurogenesis, whereas their role in gliogenesis is unknown. Here, we show that the expression of BAF155 and BAF170 is essential for the genesis of oligodendrocytes during brain development. We report that the ablation of BAF155 and BAF170 in the dorsal telencephalic (dTel) neural progenitors or in oligodendrocyte-producing progenitors in the ventral telencephalon (vTel) in double-conditional knockout (dcKO) mouse mutants, perturbed the process of oligodendrogenesis. Molecular marker and cell cycle analyses revealed impairment of oligodendrocyte precursor specification and proliferation, as well as overt depletion of oligodendrocytes pool in dcKO mutants. Our findings unveil a central role of BAF155 and BAF170 in oligodendrogenesis, and thus substantiate the involvement of the BAF complex in the production of oligodendrocytes in the forebrain.
Requirements of Postnatal proBDNF in the Hippocampus for Spatial Memory Consolidation and Neural Function
Authors: Sun Wei , Cheng Hong , Yang Yang , Tang Dongxin , Li Xiaolian , An Lei
Published: July 2021

Mature brain-derived neurotrophic factor (BDNF) and its downstream signaling pathways have been implicated in regulating postnatal development and functioning of rodent brain. However, the biological role of its precursor pro-brain-derived neurotrophic factor (proBDNF) in the postnatal brain remains unknown. The expression of hippocampal proBDNF was blocked in postnatal weeks, and multiple behavioral tests, Western blot and morphological techniques, and neural recordings were employed to investigate how proBDNF played a role in spatial cognition in adults. The peak expression and its crucial effects were found in the fourth but not in the second or eighth postnatal week. Blocking proBDNF expression disrupted spatial memory consolidation rather than learning or memory retrieval. Structurally, blocking proBDNF led to the reduction in spine density and proportion of mature spines. Although blocking proBDNF did not affect N-methyl-D-aspartate (NMDA) receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, the learning-induced phosphorylation of the GluN2B subunit level declined significantly. Functionally, paired-pulse facilitation, post-low-frequency stimulation (LFS) transiently enhanced depression, and GluN2B-dependent short-lasting long-term depression in the Schaffer collateral-CA1 pathway were weakened. The firing rate of pyramidal neurons was significantly suppressed around the target region during the memory test. Furthermore, the activation of GluN2B-mediated signaling could effectively facilitate neural function and mitigate memory impairment. The findings were consistent with the hypothesis that postnatal proBDNF played an essential role in synaptic and cognitive functions.
Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways
Authors: Pu Xudong , Li Xin , Cao Lili , Yue Kaiming , Zhao Panpan , Wang Xiaocen , Li Jianhua , Zhang Xichen , Zhang Nan , Zhao Zhiteng , Liang Min , Gong Pengtao
Published: July 2021

Giardia duodenalis, also known as Giardia lamblia or Giardia intestinalis, is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis–stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis–induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis.
A Preliminary Single-Cell RNA-Seq Analysis of Embryonic Cells That Express Brachyury in the Amphioxus, Branchiostoma japonicum
Authors: Satoh Noriyuki , Tominaga Hitoshi , Kiyomoto Masato , Hisata Kanako , Inoue Jun , Nishitsuji Koki
Published: July 2021

Among chordate taxa, the cephalochordates diverged earlier than urochordates and vertebrates; thus, they retain unique, primitive developmental features. In particular, the amphioxus notochord has muscle-like properties, a feature not seen in urochordates or vertebrates. Amphioxus contains two Brachyury genes, Bra1 and Bra2. Bra2 is reportedly expressed in the blastopore, notochord, somites, and tail bud, in contrast to a low level of Bra1 expression only in notochord. To distinguish the expression profiles of the two Brachyury genes at the single-cell level, we carried out single-cell RNA-seq (scRNA-seq) analysis using the amphioxus, Branchiostoma japonicum. This scRNA-seq analysis classified B. japonicum embryonic cells into 15 clusters at developmental stages from midgastrula to early swimming larva. Brachyury was expressed in cells of clusters 4, 5, 8, and 9. We first confirmed that cluster 8 comprises cells that form somites since this cluster specifically expresses four myogenic factor genes. Cluster 9 contains a larger number of cells with high levels of Bra2 expression and a smaller number of cells with Bra1 expression. Simultaneous expression in cluster 9 of tool-kit genes, including FoxA, Goosecoid, and hedgehog, showed that this cluster comprises cells that form the notochord. Expression of Bra2, but not Bra1, in cells of clusters 4 and 5 at the gastrula stage together with expression of Wnt1 and Caudal indicates that clusters 4 and 5 comprise cells of the blastopore, which contiguously form the tail bud. In addition, Hox1, Hox3, and Hox4 were highly expressed in Bra2-expressing clusters 4, 5, 8, and 9 in a temporally coordinated manner, suggesting roles of anterior Hox genes in specification of mesodermal organs, including somites, notochord, and tail bud. This scRNA-seq analysis therefore highlights differences between the two Brachyury genes in relation to embryonic regions in which they are expressed and their levels of expression. Bra2 is the ancestral Brachyury in amphioxus, since expression in the blastopore is shared with other deuterostomes. On the other hand, Bra1 is a duplicate copy and likely evolved a supplementary function in notochord and somite formation in the Branchiostoma lineage.
GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity
Authors: Kristensen Kristian Kølby , Leth-Espensen Katrine Zinck , Kumari Anni , Grønnemose Anne Louise , Lund-Winther Anne-Marie , Young Stephen G. , Ploug Michael
Published: July 2021

Intravascular processing of triglyceride-rich lipoproteins (TRLs) is crucial for delivery of dietary lipids fueling energy metabolism in heart and skeletal muscle and for storage in white adipose tissue. During the last decade, mechanisms underlying focal lipolytic processing of TRLs along the luminal surface of capillaries have been clarified by fresh insights into the functions of lipoprotein lipase (LPL); LPL’s dedicated transporter protein, glycosylphosphatidylinositol-anchored high density lipoprotein–binding protein 1 (GPIHBP1); and its endogenous inhibitors, angiopoietin-like (ANGPTL) proteins 3, 4, and 8. Key discoveries in LPL biology include solving the crystal structure of LPL, showing LPL is catalytically active as a monomer rather than as a homodimer, and that the borderline stability of LPL’s hydrolase domain is crucial for the regulation of LPL activity. Another key discovery was understanding how ANGPTL4 regulates LPL activity. The binding of ANGPTL4 to LPL sequences adjacent to the catalytic cavity triggers cooperative and sequential unfolding of LPL’s hydrolase domain resulting in irreversible collapse of the catalytic cavity and loss of LPL activity. Recent studies have highlighted the importance of the ANGPTL3–ANGPTL8 complex for endocrine regulation of LPL activity in oxidative organs (e.g., heart, skeletal muscle, brown adipose tissue), but the molecular mechanisms have not been fully defined. New insights have also been gained into LPL–GPIHBP1 interactions and how GPIHBP1 moves LPL to its site of action in the capillary lumen. GPIHBP1 is an atypical member of the LU (Ly6/uPAR) domain protein superfamily, containing an intrinsically disordered and highly acidic N-terminal extension and a disulfide bond–rich three-fingered LU domain. Both the disordered acidic domain and the folded LU domain are crucial for the stability and transport of LPL, and for modulating its susceptibility to ANGPTL4-mediated unfolding. This review focuses on recent advances in the biology and biochemistry of crucial proteins for intravascular lipolysis.
N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients
Authors: Zhang Peiling , Liu Guolong , Lu Lin
Published: July 2021

Background

Colon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.

Materials and Methods

The m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.

Results

We identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.

Conclusion

In this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.
Is RAS the Link Between COVID-19 and Increased Stress in Head and Neck Cancer Patients?
Authors: Iftikhar Anem , Islam Mohammad , Shepherd Simon , Jones Sarah , Ellis Ian
Published: July 2021

The COVID-19 pandemic emerged as a largely unexplained outbreak of pneumonia cases, in Wuhan City, China and rapidly spread across the world. By 11th March 2020, WHO declared it as a global pandemic. The resulting restrictions, to contain its spread, demanded a momentous change in the lifestyle of the general population as well as cancer patients. This augmented negative effects on the mental health of patients with head and neck cancer (HNC), who already battle with the stress of cancer diagnosis and treatment. The causative agent of COVID-19, SARS-CoV2, gains entry through the Angiotensin converting enzyme 2 (ACE2) receptor, which is a component of the Renin Angiotensin System (RAS). RAS has been shown to influence cancer and stress such that it can have progressive and suppressive effects on both. This review provides an overview of SARS-CoV2, looks at how the RAS provides a mechanistic link between stress, cancer and COVID-19 and the probable activation of the RAS axis that increase stress (anxiogenic) and tumor progression (tumorigenic), when ACE2 is hijacked by SARS-CoV2. The mental health crises brought about by this pandemic have been highlighted in many studies. The emerging links between cancer and stress make it more important than ever before to assess the stress burden of cancer patients and expand the strategies for its management.
Genome Editing Technologies as Cellular Defense Against Viral Pathogens
Authors: Zhang Yingzi , Li Mo
Published: July 2021

Viral infectious diseases are significant threats to the welfare of world populations. Besides the widespread acute viral infections (e.g., dengue fever) and chronic infections [e.g., those by the human immunodeficiency virus (HIV) and hepatitis B virus (HBV)], emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose great challenges to the world. Genome editing technologies, including clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), have played essential roles in the study of new treatment for viral infectious diseases in cell lines, animal models, and clinical trials. Genome editing tools have been used to eliminate latent infections and provide resistance to new infections. Increasing evidence has shown that genome editing-based antiviral strategy is simple to design and can be quickly adapted to combat infections by a wide spectrum of viral pathogens, including the emerging coronaviruses. Here we review the development and applications of genome editing technologies for preventing or eliminating infections caused by HIV, HBV, HPV, HSV, and SARS-CoV-2, and discuss how the latest advances could enlighten further development of genome editing into a novel therapy for viral infectious diseases.
Nitric Oxide-Releasing Nanoparticles Are Similar to Efinaconazole in Their Capacity to Eradicate Trichophyton rubrum Biofilms
Authors: Costa-Orlandi Caroline Barcelos , Martinez Luis R. , Bila Níura Madalena , Friedman Joel M. , Friedman Adam J. , Mendes-Giannini Maria José S. , Nosanchuk Joshua D.
Published: July 2021

Filamentous fungi such as Trichophyton rubrum and T. mentagrophytes, the main causative agents of onychomycosis, have been recognized as biofilm-forming microorganisms. Nitric oxide-releasing nanoparticles (NO-np) are currently in development for the management of superficial and deep bacterial and fungal infections, with documented activity against biofilms. In this context, this work aimed to evaluate, for the first time, the in vitro anti-T. rubrum biofilm potential of NO-np using standard ATCC MYA-4438 and clinical BR1A strains and compare it to commonly used antifungal drugs including fluconazole, terbinafine and efinaconazole. The biofilms formed by the standard strain produced more biomass than those from the clinical strain. NO-np, fluconazole, terbinafine, and efinaconazole inhibited the in vitro growth of planktonic T. rubrum cells. Similarly, NO-np reduced the metabolic activities of clinical strain BR1A preformed biofilms at the highest concentration tested (SMIC50 = 40 mg/mL). Scanning electron and confocal microscopy revealed that NO-np and efinaconazole severely damaged established biofilms for both strains, resulting in collapse of hyphal cell walls and reduced the density, extracellular matrix and thickness of the biofilms. These findings suggest that biofilms should be considered when developing and testing new drugs for the treatment of dermatophytosis. Development of a biofilm phenotype by these fungi may explain the resistance of dermatophytes to some antifungals and why prolonged treatment is usually required for onychomycosis.
The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children
Authors: Zheng Yan , Hua Lingling , Zhao Qiannan , Li Mengyao , Huang Meixia , Zhou Yunlian , Wang Yingshuo , Chen Zhimin , Zhang Yuanyuan
Published: July 2021

Objective

Mycoplasma pneumoniae pneumonia (MPP) is an important disease in children. Studies have demonstrated that the levels of D-dimer are elevated in some children with MPP, especially those with thrombotic complications. However, the potential association between MPP and D-dimer remains unclear. In our study, we sought to explore the relationship between the levels of plasma D-dimer and clinical characteristics of MPP patients.

Methods

Retrospective analysis was conducted on 356 patients who were hospitalized in our hospital for MPP between January 1, 2017, and December 31, 2019. According to the peak value of D-dimer, patients were divided into three groups: the normal group (D-dimer<0.55 mg/L), the mild-moderately elevated group (D-dimer 0.55–5.5 mg/L) and the severely elevated group (D-dimer >5.5 mg/L). The demographic and clinical information, radiological findings, laboratory data, and treatments of patients were compared among different groups.

Results

106 patients were in the normal group, 204 patients were in the mild-moderately elevated group, and 46 patients were in the severely elevated group. More severe clinical and radiographic manifestations, longer length of fever, hospital stay and antibiotic therapy duration, higher incidences of extra-pulmonary complications, refractory MPP (RMPP), severe MPP (SMPP) were found in the elevated group, when compared with the normal group (P<0.01). Meanwhile, we found that the percentage of neutrophil (N%) and CD8+ lymphocyte (CD8+%), C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ) trended higher with increasing D-dimer, whereas the percentage of lymphocyte (L%) and prealbumin (PAB) trended lower (P<0.01). In addition, the proportions of patients requiring oxygen therapy, glucocorticoid, bronchoscopy, immunoglobulin use, thoracentesis, or ICU admission were significantly higher in the severely elevated group than those in the other two groups (P<0.01). Correlation analysis showed that N%, L%, CRP, LDH, IL-10, length of fever, length of stay, and length of antibiotic therapy had strong correlations with the level of D-dimer.

Conclusions

MPP patients with higher levels of D-dimer had more severe clinical manifestations and needed longer duration of treatment, which might be closely related to the severity of lung inflammation after MP infection.
Peri-procedural Trans-esophageal Echocardiographic Sizing of the Native Left Ventricular Outflow Tract During Edwards INTUITY Valve Implantation
Authors: Lim Kevin , Ho Yan Kit , Chow Simon Chi Ying , Fujikawa Takuya , Lee Alex Pui-Wai , Wong Randolph Hung Leung
Published: July 2021

Background: The Edwards INTUITY rapid deployment valve was anchored on the left ventricular outflow tract (LVOT) by radial force akin to transcatheter balloon-expandable valves. This design feature facilitates minimally invasive and complex procedures but comes at the price of compressing the atrioventricular conduction bundle and potential requirement for pacemaker implantation.

Methods: A retrospective observational study was conducted on 30 consecutive patients who received the INTUITY valve at our institution from August 2018 to January 2021. Demographical, clinical, and echocardiographic parameters were collected for 90 days post-operatively. The diameter of the native LVOT at the landing site of the sub-annular stent was retrospectively measured using archived trans-esophageal echocardiographic images. A line was drawn from the inner edge of the septal endocardium to the inner edge of the anterior mitral leaflet in mid-systole, parallel to the aortic annulus, 6–8 mm apical to the aortic annulus depending on the valve size and the corresponding stent length. Risk factors associated with new onset conduction disturbances, defined as the occurrence of bundle branch block or complete heart block, were analyzed.

Results: Operative mortality was 3.3%. Pre-operatively, permanent pacemakers were required for two patients who were excluded from the subsequent analysis. New onset conduction disturbances occurred in four of the remaining 28 patients (14.3%). This included two incidences of persistent left bundle branch block and two incidences of permanent pacemaker implantation due to complete heart block. Univariate analysis identified over-sizing of the native LVOT by 5 mm or more as a significant risk factor associated with conduction disturbance.

Conclusion: During INTUITY vale implantation, in addition to the aortic annulus, the landing site of the sub-annular stent within the native LVOT should also be sized pre-bypass. Over-sizing the native LVOT by 5 mm or more was associated with an increased risk of new onset conduction disturbances and should be avoided.
Softening of Temperate Ice by Interstitial Water
Authors: Adams Conner J. C. , Iverson Neal R. , Helanow Christian , Zoet Lucas K. , Bate Charlotte E.
Published: July 2021

Ice at depth in ice-stream shear margins is thought to commonly be temperate, with interstitial meltwater that softens ice. Models that include this softening extrapolate results of a single experimental study in which ice effective viscosity decreased by a factor of ∼3 over water contents of ∼0.01–0.8%. Modeling indicates this softening by water localizes strain in shear margins and through shear heating increases meltwater at the bed, enhancing basal slip. To extend data to higher water contents, we shear lab-made ice in confined compression with a large ring-shear device. Ice rings with initial mean grain sizes of 2–4 mm are kept at the pressure-melting temperature and sheared at controlled rates with peak stresses of ∼0.06–0.20 MPa, spanning most of the estimated shear-stress range in West Antarctic shear margins. Final mean grain sizes are 8–13 mm. Water content is measured by inducing a freezing front at the ice-ring edges, tracking its movement inward with thermistors, and fitting the data with solutions of the relevant Stefan problem. Results indicate two creep regimes, below and above a water content of ∼0.6%. Comparison of effective viscosity values in secondary creep with those of tertiary creep from the earlier experimental study indicate that for water contents of 0.2–0.6%, viscosity in secondary creep is about twice as sensitive to water content than for ice sheared to tertiary creep. Above water contents of 0.6%, viscosity values in secondary creep are within 25% of those of tertiary creep, suggesting a stress-limiting mechanism at water contents greater than 0.6% that is insensitive to ice fabric development in tertiary creep. At water contents of ∼0.6–1.7%, effective viscosity is independent of water content, and ice is nearly linear-viscous. Minimization of intercrystalline stress heterogeneity by grain-scale melting and refreezing at rates that approach an upper bound as grain-boundary water films thicken might account for the two regimes.
Is Science for Everyone? Exploring Intersectional Inequalities in Connecting With Science
Authors: Seebacher Lisa M. , Vana Irina , Voigt Christian , Tschank Juliet
Published: July 2021

Several studies have investigated the way learners connect with science, re-emphasising persisting inequalities in science learning. This article combines the concept of intersectionality with the theoretical lens of science learning ecologies to focus on inequalities in connecting with science: Which factors influence the formation of a positive science attitude of young learners and how does the social background of young learners influence their opportunities of connecting with science, focusing on the intersections of class and gender? Based on a quantitative survey among 1,486 visitors of non-formal science education offers aged between 8 and 21, we analyze important factors for the development of a positive science attitude and investigate structural inequalities. The intersectional perspective was implemented in the sampling, survey design as well as its analysis. Using composite indicators of age and gender as well as gender and educational capital, we avoid a homogenisation of broadly defined groups. The results highlight that the development of a highly positive science attitude–as identified in a stepwise logistic regression model–is linked to supportive social environments, intrinsic motivation, science learning in school as well as regular engagement in arts-based learning, and self-directed science learning. The learning ecology perspective illustrates the influence of school on science attitudes in general. From an intersectional perspective, however, our findings demonstrate that the persistence of an androcentric and classist concept of science is not compatible with every learning ecology; male learners from educationally affluent backgrounds are most likely to enjoy science learning and see how science relates to their everyday realities. In turn, however, not only female learners with lower educational capital but also male learners with lower educational capital might find it more difficult to connect with science. The intersectional approach unveiled the multiple ways educational capital and gender shape individual learning ecologies. More equitable science learning spaces and offers have to adapt to a diversity of needs and preferences in order to make science activities enjoyable for all.