bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil-Lymphocyte Ratio as a Prognostic Marker for Chemotherapy in Advanced Lung Cancer
Authors: Liu Zhu-Lin , Zeng Ting-Ting , Zhou Xiao-Juan , Ren Ya-Nv , Zhang Lei , Zhang Xin-Xing , Ding Zhen-Yu
Published: July 2016

Background

Lung cancer ranks first both in morbidity and mortality in malignancies, but prognostic biological markers are lacking. The neutrophil-lymphocyte ratio (NLR) was proposed as a convenient biological marker. This study aimed to explore the prognostic value of NLR in advanced non-small cell lung cancer (NSCLC).

Methods

This retrospective study screened patients admitted from October 2007 to October 2014. Patients had histopathologically confirmed, treatment-naïve, metastatic NSCLC, and were prescribed platinum doublet chemotherapy. NLR and demographic data were collected, together with the outcome of chemotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression model.

Results

A total of 325 patients were enrolled. The cutoff value for NLR (3.19) was determined by receiver operator characteristic analysis. Patients were dichotomized into high (≥3.19) and low (<3.19) NLR groups. Both groups had similar demographic features. However, the low-NLR group had longer PFS (6.1 months) and OS (22.3 months) than the high-NLR group (5.1 months, p = 0.002; 13.1 months, p<0.001, respectively). Multivariate analysis confirmed that NLR was inversely related to the prognosis of these patients (HR = 1.684, 95%: 1.297-2.185, p<0.001).

Conclusions

This study argues that NLR is a convenient prognostic biological marker for advanced NSCLC patients treated with first-line chemotherapy and warrants further validation.
How allomorphic is English article allomorphy?
Authors: Pak Marjorie
Published: July 2016

The question of how to distinguish allomorphy from phonology plays a central role in morphological theory. While English a/an has been cited as a hallmark case of “phrasal” allomorphy, the parallel alternation between /.i/ and /.ə/ in the English definite article (/.ə/ book, /.i/ apple) has not received as much attention. This paper provides a formal analysis of English a/an and /.i/~/.ə/. I argue that: (i) /.i/~/.ə/ is not allomorphic, but is derived by the same phonological rules (tensing and vowel-reduction) as other V~ə alternations in English; and (ii) a/an involves a two-tiered derivation: first allomorphy establishes a basic split between V and Vn; then the same phonological rules involved in the (tensing and vowel-reduction) derive the four surface variants /ej/, /æn/, /ə/, and /ən/. In other words, in addition to its basic n~Ø alternation, a/an also participates in the same V~ə alternation as other strong-weak function-word pairs in English (/.i/~/.ə/ in the, /kæn/~/kən/ in can, etc.). This two-tiered serialist approach is incompatible with analyses of a/an as surface phonological optimization, or TETU (Mascaró 1996b). Accordingly, I provide evidence from emphatic glottal stops, /h/‑deletion and pause-fillers showing that despite initial appearances, neither a/an nor /.i/~/.ə/ is driven by surface syllable well-formedness constraints.
Interferon-free treatment of chronic hepatitis C virus infection in patients with inherited bleeding disorders
Authors: Schiefke Ingolf , Stein Kerstin , Berg Thomas , Kullig Ulrike , Ende Katrin , Wiegand Johannes
Published: July 2016

Chronic hepatitis C virus (HCV) infection causes significant mortality in patients with inherited bleeding disorders, however, data of interferon-free antiviral regimes are scarce in this population. Patients, methods: Reallife data of interferon-free therapies of 18 patients with inherited bleeding disorders and chronic HCV genotype 1 infection (94% male, liver cirrhosis Child A/B n = 4/1). Results: Treatment naïve patients were treated for eight weeks with sofosbuvir (SOF)/ledipasvir (n = 3) or for 12 weeks with SOF/ledipasvir (n = 4), SOF/ledipasvir/ribavirin (n = 1), or paritaprevir/r, ombitasvir, dasabuvir (n = 1). Treatment experienced patients without cirrhosis received SOF/ledipasvir (n = 3) or paritaprevir/r, ombitasvir, dasabuvir ± ribavirin (n = 2) for 12 weeks. Re-treated cirrhotic individuals were treated for 24 weeks with SOF/ledipasvir (n = 2) and SOF/daclatasvir (n = 1), or for 12 weeks SOF/simeprevir/1200 mg/d ribavirin (n = 1). Sustained virologic response (SVR-12) was achieved by 17/18 individuals without severe on-treatment side effects. Conclusions: In real-life, HCV-infected patients with inherited bleeding disorders can be effectively and safely treated with interferon- free therapies.
New records of Skyttea nitschkei from the Augustów Forest in Poland
Authors: Matwiejuk Anna
Published: July 2016

The paper presents data about an interesting lichenicolous fungus Skyttea nitschkei (Körb.) Sherwood, D. Hawksw. & Coppins reported for the first time from Poland. Material described was collected by the author in 2014 in the Augustów Forest on thalli of Thelotrema lepadinum grown on the bark of Quercus robur. The stand was located in moist fertile oak-linden-hornbeam forest Tilio-Carpinetum with old Q. robur, Carpinus betulus, Alnus glutinosa, and Picea abies. Skyttea nitschkei is compared with some other species of the genus Skyttea, namely S. carboneae and S. tavaresae. Diagnostic characters of Skyttea species with similar excipular pigments is shown. Additionally, a list of lichenicolous fungi from the Augustów Forest is also presented.
Por uma história fotográfica dos acontecimentos contemporâneos, Rio de Janeiro, 30 de junho de 1987
Authors: Mauad Ana Maria
Published: July 2016

Este artigo analisa o acontecimento histórico – “quebra-quebra” no Centro do Rio, em junho de 1987 – por meio das fotografias veiculadas em 5 jornais do Rio de Janeiro e 1 de Niterói, no dia seguinte ao acontecimento, 1o de julho de 1987. Observa-se, preliminarmente, a origem da preocupação historiográfica, em que os acontecimentos foram reabilitados para a análise histórica, sobretudo pela forma como a fotografia foi convocada para seu estudo. A reconstrução da história fotográfica do evento de 1987 apoia-se nas noções de fotografia pública e espaço público visual, para analisar os sentidos do acontecimento produzidos pelos jornais da cidade do Rio de Janeiro e avaliar o papel desempenhado pelo fotojornalismo na produção do fato histórico. Palavras-chave: Fotografia na Historiografia; Rio de Janeiro (RJ) - História – 1987; Espaços Públicos - Rio de Janeiro.
Propondo o alisamento do espaço: disputas em torno da “Manaus moderna”
Authors: Silva Patrícia Rodrigues
Published: July 2016

Este artigo apresenta uma reflexão acerca de projetos voltados para a Área denominada de “Manaus Moderna” na cidade de Manaus/AM, que visam a criar atividades definindo os usos do espaço enquanto cenário. Essa área se coloca como um espaço de disputa por diversos interesses na cidade de Manaus. O foco do artigo recai sobre as transformações propostas para a área da Manaus Moderna e nas questões vividas por essa espacialidade atualmente, pois entende-se que ali são experimentadas as pressões e lutas de classes vivenciadas na cidade como um todo, e, portanto, estão evidenciadas as tensões do viver na cidade. Palavras-chave: Manaus - Cidade, Memórias, História, Fotografias, Fontes Orais.
As redes políticas de solidariedade na América Latina
Authors: Badan Ribeiro Maria Claudia
Published: July 2016

A pesquisa que ampara este artigo teve como foco investigar os graus de relações políticas estabelecidas entre o movimento revolucionário brasileiro e o exterior em países que tanto favoreceram a luta de brasileiros, como serviram de acolhimento aos exilados. A solidificação destes acordos ocorreu no bojo de um contexto explosivo de transformação social, dando origem a grupos que substituíram os conflitos armados tradicionais do passado por estruturas políticas paralelas e difusas que estiveram na emergência de uma variedade de movimentos de resistência armada existentes na América Latina, África e Europa. Palavras-chave: Ditadura e Ditadores – América Latina, Exilio – América Latina, Movimentos Sociais.
Diagnostic potential of tumor DNA from ovarian cyst fluid
Authors: Wang Yuxuan , Sundfeldt Karin , Mateoiu Constantina , Shih Ie-Ming , Kurman Robert J , Schaefer Joy , Silliman Natalie , Kinde Isaac , Springer Simeon , Foote Michael , Kristjansdottir Björg , James Nathan , Kinzler Kenneth W , Papadopoulos Nickolas , Diaz Luis A , Vogelstein Bert
Published: July 2016

We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.
Under pressure
Authors: Hammes Ulrich Z
Published: July 2016

The movement of water by osmosis causes pressure differences that drive the transport of sugars over long distances in plants.
When communities collide
Authors: Merritt Jason , Kuehn Seppe
Published: July 2016

A new model demonstrates how microbial communities can survive encounters with other communities as a cohesive group, even in the complete absence of cooperation.
Reexamination of Fermi level pinning for controlling Schottky barrier height at metal/Ge interface
Authors: Nishimura Tomonori , Yajima Takeaki , Toriumi Akira
Published: July 2016

The element metal/germanium (Ge) interface exhibits a strong Fermi level pinning (FLP), which is usually characterized on the basis of Ge side semiconductor properties. In this work, we demonstrate that metal properties significantly affect the Schottky barrier height (SBH) on Ge. Metallic germanides show both FLP alleviation and a clear substrate orientation dependence of SBH on Ge, despite the nearly perfect FLP and very slight orientation dependence in the element metal case. As a result, ohmic characteristics are observed at germanide/n-Ge (111) junctions. The metal properties required to alleviate the FLP on Ge are also discussed.
Integration of GaAs, GaN, and Si-CMOS on a common 200 mm Si substrate through multilayer transfer process
Authors: Lee Kwang Hong , Bao Shuyu , Zhang Li , Kohen David , Fitzgerald Eugene , Tan Chuan Seng
Published: July 2016

The integration of III–V semiconductors (e.g., GaAs and GaN) and silicon-on-insulator (SOI)-CMOS on a 200 mm Si substrate is demonstrated. The SOI-CMOS donor wafer is temporarily bonded on a Si handle wafer and thinned down. A second GaAs/Ge/Si substrate is then bonded to the SOI-CMOS-containing handle wafer. After that, the Si from the GaAs/Ge/Si substrate is removed. The GaN/Si substrate is then bonded to the SOI–GaAs/Ge-containing handle wafer. Finally, the handle wafer is released to realize the SOI–GaAs/Ge/GaN/Si hybrid structure on a Si substrate. By this method, the functionalities of the materials used can be combined on a single Si platform.
Entrepreneurship and Adolescents
Authors: Santana Vega Lidia E. , González-Morales Olga , García Luis Feliciano
Published: July 2016

This work studied the entrepreneurial aspirations of 3,987 adolescents regarding self-employment and the influence of gender, age, nationality, type of school, location of the school, educational level and performance. The Logit model is used to analyze the data. The results indicate that the pupils’ aspirations to be self-employed increase in the case of foreigners, of studying in a state school, of having a lower educational level and of demonstrating a low academic performance. The results were not statistically significant for the gender and age variables. The curriculum and guidance programmes need to promote a spirit of entrepreneurship and creativity in young people
Heritage, Second-Language and Native Speakers’ Intuitions on Deictic Verbs in Spanish: Beyond the Linguist’s Intuitions
Authors: Chui Daniel
Published: July 2016

Previous analyses of the Spanish deictic verbs venir ‘to come’, ir ‘to go’, traer ‘to bring’ and llevar ‘to take’ have drawn upon Fillmore’s (1975) series of lectures on deixis in noting that speakers of Spanish forbid the use of the verbs venir and traer to express movement towards the hearer. Under this egocentric view (Beinhauer, 1940; Ibañez, 1983), the Spanish verbs venir and traer can only be used to describe movement towards the speaker’s location. Little experimental research has been done, however, to confirm the extent to which heritage and second language (L2) speakers of the language conform to this pattern. The present study gathered data on the deictic preferences of bilingual, heritage speakers of Spanish and English (HS) and compared this data with that of L2 and monolingual native speakers of Spanish (NS). 74 participants, consisting of 12 NS, 34 HS, and 29 L2 speakers, assessed the grammaticality of 20 stimulus items that contained prescriptively correct and incorrect usages of the deictic verbs venir, traer, llevar and ir. Both HS and L2 speakers made significantly more errors than NS when the direction expressed in the stimulus was oriented towards the hearer, suggesting both groups may benefit from instruction on this topic.
Towards School Transformation. Evaluation of a Coexistence Program from the Voice of Students and Teachers
Authors: Grau Roser , García-Raga Laura , López-Martín Ramón
Published: July 2016

Learning to coexist continues to be one of the challenges faced by the current educational system, especially for those schools located in contexts at risk of social exclusion where the violence rate increases on a daily basis. The main aim sought by the present study consists in assessing the impact of a program developed at an educational center located in a vulnerable neighborhood of the city of Valencia (Spain). It is a quasi-experimental, pretest-posttest research with a control group that involved a total of 109 teachers and students. It deserves to be highlighted that this paper forms part of a broader research initiative, for which reason the results obtained in the qualitative part through the implementation of a content analysis are presented. The results show the success of the program applied in accordance with the perceptions of the teachers and students involved, who state that all the program strategies have significantly improved school coexistence.
A Clinical Analysis of Vitamin D Status in Patients Before Spinal Surgery
Authors: Li Qingqing , Zhang Jianwei , Chen Jian , Fan Jin , Jiang Tao , Yin Jian , Zhou Wei , Yu Lipeng , Yin Guoyong
Published: July 2016

The goal of this paper was to study preoperative concentrations of vitamin D in patients undergoing spinal surgery and analyze relevant risk factors associated with vitamin D deficiency. Vitamin D plays an important role in maintaining normal functions of skeletal muscles, and vitamin D insufficiency or deficiency may affect outcomes of spinal surgery patients. A retrospective analysis was conducted on 503 patients undergoing spinal surgery in the First Affiliated Hospital with Nanjing Medical University from September 2012 to October 2013. Preoperative concentrations of serum 25-hydroxyvitamin D [25(OH)D] were measured. Normal vitamin D was defined as a serum 25(OH)D level ≥ 32 ng/mL, vitamin D insufficiency as ≥20 and <32 ng/mL, and vitamin D deficiency as <20 ng/mL. Relevant risk factors associated with vitamin D insufficiency and deficiency were analyzed. In 503 spinal surgery patients, rate of vitamin D deficiency and insufficiency was 71.4% and 23.9%. Rate of vitamin D deficiency in female patients was significantly higher than that in male (P < 0.001). Rate of vitamin D deficiency in patients with high body mass index (P = 0.009) or patients with smoking habit (P < 0.001) was much higher than other patients. Multivariate analysis demonstrated that female (P < 0.001), smoking (P = 0.005), and winter (P = 0.001) were potential risk factors for vitamin D deficiency. Screening preoperative vitamin D status and relevant treatment should be reinforced in spine surgery patients.
Progesterone induces the expression of lipocalin‐2 through Akt‐c‐Myc pathway during mouse decidualization
Authors: Liu Yue‐Fang , Deng Wen‐Bo , Li Shu‐Yun , Yao Mei‐Nan , Liu Jie , Dou Hai‐Tin , Zhao Meng‐Long , Yang Zeng‐Ming , Liang Xiao‐Huan
Published: July 2016

Lipocalin‐2 (Lcn2) is a small glycoprotein involved in a number of biological processes such as inflammation and antibacterial response. In our study, Lcn2 is expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy. The expression of Lcn2 in stromal cells is under the control of progesterone through Akt‐c‐Myc signaling pathway. Data from Lcn2 knockdown and recombinant protein treatments indicate that Lcn2 promotes mPGES‐1 expression in stromal cells. The expression of Lcn2 and mPGES‐1 is strongly stimulated by lipopolysaccharide (LPS), indicating that Lcn2 mediates LPS‐induced inflammation. These findings shed light on the role of Lcn2 during decidualization.
Recent advances quantifying the large wood dynamics in river basins: New methods and remaining challenges
Authors: Ruiz‐Villanueva Virginia , Piégay Hervé , Gurnell Angela M. , Marston Richard A. , Stoffel Markus
Published: July 2016

Large wood is an important physical component of woodland rivers and significantly influences river morphology. It is also a key component of stream ecosystems. However, large wood is also a source of risk for human activities as it may damage infrastructure, block river channels, and induce flooding. Therefore, the analysis and quantification of large wood and its mobility are crucial for understanding and managing wood in rivers. As the amount of large‐wood‐related studies by researchers, river managers, and stakeholders increases, documentation of commonly used and newly available techniques and their effectiveness has also become increasingly relevant as well. Important data and knowledge have been obtained from the application of very different approaches and have generated a significant body of valuable information representative of different environments. This review brings a comprehensive qualitative and quantitative summary of recent advances regarding the different processes involved in large wood dynamics in fluvial systems including wood budgeting and wood mechanics. First, some key definitions and concepts are introduced. Second, advances in quantifying large wood dynamics are reviewed; in particular, how measurements and modeling can be combined to integrate our understanding of how large wood moves through and is retained within river systems. Throughout, we present a quantitative and integrated meta‐analysis compiled from different studies and geographical regions. Finally, we conclude by highlighting areas of particular research importance and their likely future trajectories, and we consider a particularly underresearched area so as to stress the future challenges for large wood research.
Model simulations of flood and debris flow timing in steep catchments after wildfire
Authors: Rengers F. K. , McGuire L. A. , Kean J. W. , Staley D. M. , Hobley D. E. J.
Published: July 2016

Debris flows are a typical hazard on steep slopes after wildfire, but unlike debris flows that mobilize from landslides, most postwildfire debris flows are generated from water runoff. The majority of existing debris flow modeling has focused on landslide‐triggered debris flows. In this study we explore the potential for using process‐based rainfall‐runoff models to simulate the timing of water flow and runoff‐generated debris flows in recently burned areas. Two different spatially distributed hydrologic models with differing levels of complexity were used: the full shallow water equations and the kinematic wave approximation. Model parameter values were calibrated in two different watersheds, spanning two orders of magnitude in drainage area. These watersheds were affected by the 2009 Station Fire in the San Gabriel Mountains, CA, USA. Input data for the numerical models were constrained by time series of soil moisture, flow stage, and rainfall collected at field sites, as well as high‐resolution lidar‐derived digital elevation models. The calibrated parameters were used to model a third watershed in the burn area, and the results show a good match with observed timing of flow peaks. The calibrated roughness parameter (Manning'sn) was generally higher when using the kinematic wave approximation relative to the shallow water equations, and decreased with increasing spatial scale. The calibrated effective watershed hydraulic conductivity was low for both models, even for storms occurring several months after the fire, suggesting that wildfire‐induced changes to soil‐water infiltration were retained throughout that time. Overall, the two model simulations were quite similar suggesting that a kinematic wave model, which is simpler and more computationally efficient, is a suitable approach for predicting flood and debris flow timing in steep, burned watersheds.
Impact of the Antarctic bottom water formation on the Weddell Gyre and its northward propagation characteristics in GFDL CM2.1 model
Authors: Zhang Liping , Delworth Thomas L.
Published: July 2016

The impact of Antarctic bottom water (AABW) formation on the Weddell Gyre and its northward propagation characteristics are studied using a 4000 year long control run of the GFDL CM2.1 model as well as sensitivity experiments. In the control run, the AABW cell and Weddell Gyre are highly correlated when the AABW cell leads the Weddell Gyre by several years, with an enhanced AABW cell corresponding to a strengthened Weddell Gyre and vice versa. An additional sensitivity experiment shows that the response of the Weddell Gyre to AABW cell changes is primarily attributed to interactions between the AABW outflow and ocean topography, instead of the surface wind stress curl and freshwater anomalies. As the AABW flows northward, it encounters topography with steep slopes that induce strong downwelling and negative bottom vortex stretching. The anomalous negative bottom vortex stretching induces a cyclonic barotropic stream function over the Weddell Sea, thus leading to an enhanced Weddell Gyre. The AABW cell variations in the control run have significant meridional coherence in density space. Using passive dye tracers, it is found that the slow propagation of AABW cell anomalies south of 35°S corresponds to the slow tracer advection time scale. The dye tracers escape the Weddell Sea through the western limb of the Weddell Gyre and then go northwestward to the Argentine Basin through South Sandwich Trench and Georgia Basin. This slow advection by deep ocean currents determines the AABW cell propagation speed south of 35°S. North of 35°S the propagation speed is determined both by advection in the deep western boundary current and through Kelvin waves.
New perspectives for noble gases in oceanography
Authors: Aeschbach Werner
Published: July 2016

Conditions prevailing in regions of deep water formation imprint their signature in the concentrations of dissolved noble gases, which are conserved in the deep ocean. Such “recharge conditions” including temperature, salinity, and interactions with sea ice are important in view of ocean‐atmosphere CO2 partitioning. Noble gases, especially the temperature sensitive Kr and Xe, are well‐established tracers to reconstruct groundwater recharge conditions. In contrast, tracer oceanography has traditionally focused on He isotopes and the light noble gases Ne and Ar, which could be analyzed at the required high precision. Recent developments of analytical and data interpretation methods now provide fresh perspectives for noble gases in oceanography.
Unique Characteristics of Cell Division in Vascular Plants
Authors: Chabouté Marie‐Edith , Schmit Anne‐Catherine
Published: July 2016

In eukaryotes, both microtubules (
MTs
) and microfilaments (
MFs
) are cytoskeletal polymers involved in meristematic cell proliferation. While animal cells build their
MT
arrays from structured organelles, such as centrosomes, and while they depolymerise their
MFs
and become round during mitosis, vascular plant cells lack centrosomes, maintain a filamentous actin cage around the spindle and are surrounded by a cell wall, preventing cellular mobility. During the cell cycle, plants activate specific dispersed
MT
nucleating sites, revealing successive plant‐specific cytoskeletal arrays. The
MF
meshwork surrounding the spindle eventually drives the centrifugal growth of
MTs
, which leads Golgi‐derived vesicles to fuse and separate each daughter cell during cytokinesis. The main orientation of actin fibres is parallel to that of spindle
MTs
, while a perpendicular constriction ring ensures animal daughter cell separation. However, despite the differences in their cytoskeleton behaviour and dynamics, both cell types succeed in controlled chromosome segregation.

Key Concepts

Mitosis is a short cell cycle period during which the cytoskeleton ensures balanced segregation of duplicated sister chromatids into two daughter cells.

Plant cells have to deal with their pecto‐cellulosic cell wall, constraining the orientation of the division axis in order to control morphogenesis.

In plants, primary stem cells are located in shoot and root apical meristems (SAM and RAM) and secondary growth is ensured by cambium activation.

Besides the conservation of microtubules (MTs) and actin filaments (MFs), required for successful karyokinesis and cytokinesis, respectively, in all eukaryotes, plant mitotic cells present an original cytoskeleton organisation.

All the somatic cells of vascular plants lack centrosomes, and microtubule organising centres are spread all over the nuclear envelope, at the cell cortex and along pre‐existing microtubules.

Preceding the mitotic step
per se
, maintenance of centromere/kinetochore cohesion and integrity is required for the building of a bipolar spindle and accurate chromosome segregation.

During mitosis, the activity of MT nucleating complexes (TuRCs) and MT‐associated proteins (MAPs) leads to a succession of MT arrays that reorganise in the cytoplasm: cortical MTs/perinuclear MTs/pre‐prophase band MTs/spindle MTs/phragmoplast MTs. The spindle apparatus, consisting of kinetochore fibres and interpolar MTs, is barrel‐shaped and lacks polar asters. Some of the MAPs also connect MFs.

Gamma‐tubulin containing complexes and augmin complexes participate in the nucleation of new highly dynamic MTs that ensure spindle robustness.

Actin filaments intermingle with MTs and do not depolymerise during mitosis, except in the PPB, which becomes an actin‐deplete zone (ADZ).

The cell plate expands centrifugally to the cell edges thanks to actin filaments, preceding MTs on which Golgi‐derived vesicles move towards the equator and fuse together.
Reductionism in Biology
Authors: Darden Lindley
Published: July 2016

Explanatory and methodological reductionism in biology emphasises the importance of building explanations and pursuing research at ever‐deeper levels of organisation. Integrationism, in contrast, emphasises the importance of building explanations at multiple levels of organisation or utilising findings from multiple scientific fields. Some of the perceived advantages of reduction are reviewed, but it is noted that reductionist tendencies are prone to biases and distortions in the description of biological systems. Attention to integrative strategies aids in avoiding the biases and distortions that reductionist strategies are prone to produce. Integration takes different forms: integrating levels, integrating temporally extended mechanisms, and integrating findings from different fields to solve a particular problem. One should look up and around, not just down. Integration is illustrated with cases from evolutionary theory and genetics.

Key Concepts

Reductionist research strategies have advantages in biology, whereas biases that they introduce can be countered by employing integrative strategies.

Reductive research strategies reveal hidden mechanisms, but neglect their context.

Multilevel integration provides a full explanatory account of a phenomenon.

Integrative strategies bridge different levels and different scientific fields to solve scientific problems.

Integrative strategies tie together sub‐mechanisms within a temporally extended mechanism.
Genetic Carrier Testing
Authors: Henneman Lidewij , Cornel Martina
Published: July 2016

Genetic carrier testing includes tests for the heterozygous status of a recessively inherited disorder in individuals who, although apparently healthy themselves, have a high risk of transmitting the genetic disorder to their offspring. Carrier testing will allow couples of childbearing age to make informed reproductive decisions. Genetic carrier tests are used by people who have a family history of an inherited disorder or carriership, reproductive partners of carriers and partners of individuals who have the disorder. A prerequisite for knowledge about a possible risk for relatives and the availability of testing is the dissemination of information in the family. Carrier testing can also be offered as a screening test to persons who do not have an
a priori
increased risk of being a carrier based on their family history. With new genetic testing technologies, it is possible to screen for a growing number of disorders simultaneously.

Key Concepts

Reproductive planning is the most important factor motivating genetic carrier testing.

Family disclosure of genetic information is a prerequisite to knowledge about the risk and availability of carrier testing.

Because of factors impeding the sharing of information in families and factors interfering with the decision about testing, the uptake for carrier testing in high‐risk families is often lower than expected.

To minimize (time) constraints and maximize reproductive options, carrier testing before conception is advocated.

Carrier screening is the detection of carrier status in persons who do not have an
a priori
increased risk of being a carrier based on their or their partners' personal or family history.

Rapidly evolving genetic testing technologies facilitate carrier screening for a growing number of diseases simultaneously.
Bioethics: Institutionalisation of
Authors: Engelhardt HT , Iltis Ana Smith , Jotterand Fabrice
Published: July 2016

Bioethics is a recognised discipline in the academy, an established practice within the clinic and a source of guidance for healthcare policy and the conduct of human research. As a complex of theoretical and practical undertakings, bioethics now commands an officially recognised cluster of norm‐setting and behaviour‐guiding roles that have become institutionalised elements of the scholarly, clinical, human research and public policy establishment. The integration of the antecedents of bioethics into these settings began in the 1960s but these activities were recognised under this name only at the end of the 1970s. By 1979, there was an established literature, numerous individuals who called themselves bioethicists and academic programmes engaged in bioethics. Efforts to professionalise bioethics by articulating a code of ethics and establishing practice standards are ongoing. Competing conceptions of expertise shape these efforts. Attention to bioethics internationally continues to grow, particularly as biotechnological developments raise new questions and concerns.

Key Concepts

The antecedents of bioethics emerged in the 1960s, and then the field took shape under this rubric in the 1970s.

Awareness of past abuses of human research subjects and the need to conduct more research to secure progress in medicine led to a focus on research ethics and the regulation and oversight of research.

Cultural shifts in the 1960s and 1970s that emphasised individuals' rights led to discussions about patients' rights and patient‐driven decisions.

The secularisation of U.S. society in the 1960s created space for discussions of medical morality among secular scholars who sought a secular source for moral guidance.

Bioethicists provide clinical and research ethics consultations, teach and conduct research in the academy and are involved in the creation of public policy.

Efforts to professionalise bioethics are ongoing.

Bioethics continues to seek substantive moral insight from secular sources.
Nutrigenetics
Authors: Savini Isabella , Gasperi Valeria , Catani Valeria M
Published: July 2016

In the past decades, extensive usage of omic technologies applied to nutrition has led to the concept of personalised dietary recommendations. It is now widely accepted that gene–diet interaction is a complex, bidirectional mechanism: food components can modulate the flow of genetic information by regulating genes at transcriptional, translational and post‐translational levels, whereas the individual's genotype determines specific responses to nutrient intake. Genetic variants (that represent the focus of nutrigenetic studies) influence the metabolism of almost all macro‐ and micronutrients, thus differentially impacting on human health. Although still a young field of research, nutrigenetics appears to be a promising tool for monitoring susceptibility to chronic pathologies, as well as for designing personalised nutrition in order to prevent (or eventually treat) the most common Western diet‐associated diseases.

Key Concepts

Several lines of evidence indicate that diet is a key determinant of health status and that many chronic degenerative diseases (including obesity, diabetes, cardiovascular disease, cancer, neurodegenerative diseases) could be prevented by adopting a correct lifestyle.

Nutrigenetic studies indicate that there is a different susceptibility to development of these diseases in relation to food intake, due to specific genetic variants.

Nutrigenomic studies indicate that macronutrients, micronutrients and bioactive compounds can modulate gene expression, thus affecting physical and mental health.

Gene–diet interaction is a complex network; and data interpretation is not easy, as foods contain many components usually acting in combination and dietary patterns are quite variable.

It is not easy to translate scientific evidence into nutritional advice, because the organism is complex and different environmental and genetic factors have to be taken into account, especially considering the wide interindividual variability in metabolic responses.

Although holding strong promise, personalised nutrition is far from being applicable, as much accurate research is needed before application to dietetic practice.
Plant Actin Biology
Authors: Deeks Michael J , Hussey Patrick J
Published: July 2016

Actin is a major component of the plant cytoskeleton. Filamentous actin (F‐actin) contributes to the maintenance of the internal architecture of the cell, drives cytoplasmic streaming (the movement of components around the cytosol) and contributes to the process of cell division. The biochemistry of plant actin has many similarities to that of yeast and animals, but has developed its own strategies and molecular machinery to organise actin filaments. F‐actin provides tracks for myosin molecular motors to transport organelles at high velocities, and actin is required for specific stages of vesicle trafficking that underpin cell growth and development. The means by which plant cells control the nucleation of new actin filaments from G‐actin have diverged considerably from yeast and metazoans. The unique aspects of the plant actin cytoskeleton are likely to have arisen from a combination of the environmental challenges to a sessile multicellular existence and an ancient diversification from the ancestors of the Opisthokonta and Amoebozoa model organisms from which the majority of eukaryote cytoskeletal paradigms have been established.

Key Concepts

The basic principles of actin biochemistry applicable to animals, fungi and protists are conserved in plants but there are a number of specific modifications as plants do not possess the full complement of animal actin‐binding proteins.

Actin filaments in plants have to fulfil unique functions. Actin focuses on the expansion of tip growing cells, maintains cytoarchitecture and responds to the environment (e.g. polarising in response to pathogen stimulation). During cell division actin filaments participate in all major plant‐specific arrays.

A stationary cell is NOT a physically inactive cell. Actin cables are exploited for organelle transport. Actin‐based transport tends to dominate over microtubule‐based movement. Plants utilise the fastest known type V myosin (known in plants as type XI) within the eukaryote kingdom. Polymerisation dynamics are thought to add to trafficking capabilities as low levels of antiactin drugs disrupt vesicle delivery and fusion during cell growth yet preserve myosin‐mediated transport.

Plant‐specific proteins and novel domain combinations have become established in plants to regulate the actin cytoskeleton in accordance with the demands of sessile multicellular photosynthetic autotrophy. These cytoskeletal adaptations to sedentary life within a cell wall are distinct from fungi, possibly reflecting the ancient diversification between the opisthokonts and plants.
Molecular Genetics of Macular Degeneration
Authors: Cooke Bailey Jessica N , Haines Jonathan L
Published: July 2016

Age‐related macular degeneration (AMD) is a complex disease; the presentation and progression of this disease are varied among patients as are risk factors. Genetics substantially influences risk for this disease, and the pursuit of localising genetic risk factors for AMD has been quite successful over the past decade through the application of increasingly sophisticated genomic techniques. To date, researchers have rigorously applied statistical genetic methods to reveal more than 30 genetic loci associated with AMD. Connecting these loci to functional impact on disease aetiology has proved challenging, and a great deal of knowledge remains to be elucidated about this disease in order to understand the molecular mechanisms by which loci influence AMD. We herein review the history of AMD genetics and the currently known AMD genetics loci.

Key Concepts

Age‐related macular degeneration is a major cause of blindness worldwide.

Age‐related macular degeneration is a complex phenotype.

Risk for age‐related macular degeneration is substantially influenced by genetic factors.

The
CFH
and
ARMS2
/
HTRA1
loci are the most predictive genetic indicators of age‐related macular degeneration risk.

Statistical genetic analyses have revealed more than 30 genetic loci that influence risk for age‐related macular degeneration.
Counselling Issues around Preimplantation Genetic Diagnosis
Authors: Ross Sarah
Published: July 2016

Preimplantation genetic diagnosis (PGD) is a highly specialised process that uses assisted reproductive techniques to help couples increase their chances of having a child that is unaffected by a serious known genetic disorder. It requires a multidisciplinary team of professionals including specialists in both assisted reproduction and genetics.

Before a decision by a couple to undergo PGD treatment, the counsellor needs to assess their situation, discuss their genetic risk and the process of PGD including the advantages and disadvantages, while taking into account the emotional, practical and financial issues. This should enable the couple to make an informed decision about whether PGD is the most appropriate treatment for them. Counselling opportunities arise during and after a treatment cycle ensuring that couples are supported and fully aware of the implications of decisions that need to be made at each stage of the process.

Key Concepts

Preimplantation genetic diagnosis uses assisted reproductive techniques to obtain embryos that are then tested for a known serious genetic condition, before transfer to the uterus.

Assisted reproductive techniques used in PGD involve artificially stimulating the ovaries to release large numbers of eggs, which are collected and then fertilised using
in vitro
fertilisation (IVF) or in most cases, intracytoplasmic sperm insertion (ICSI).

Genetic counselling is a communication process that focuses on the occurrence or risk of a genetic disorder in the family.

FISH analysis – fluorescent in situ hybridisation is a cytogenetic technique used to detect and localise the presence or absence of specific DNA sequences on chromosomes. It uses fluorescent probes that bind to parts of the chromosome that show a high degree of sequence similarity.

Preimplantation genetic haplotyping (PGH) involves taking a single cell and extracting DNA, which is then amplified before being used for DNA fingerprinting. PGH can be used where the exact mutation is not known or cannot be identified, as long as the correct gene is identified, because the technique scans for the presence of the genetic haplotype that is associated with the familial disease gene region.

Array CGH (comparative genomic hybridisation) is a laboratory technique used to look for alterations in chromosomes that are too small to see down a microscope.
Plant Virus
RNA
Replication
Authors: Carbonell Alberto , García Juan Antonio , Simón‐Mateo Carmen , Hernández Carmen
Published: July 2016

Plant RNA (ribonucleic acid) viruses are obligate intracellular parasites with single‐stranded (ss) or double‐stranded RNA genome(s) generally encapsidated but rarely enveloped. For viruses with ssRNA genomes, the polarity of the infectious RNA (positive or negative) and the presence of one or more genomic RNA segments are the features that mostly determine the molecular mechanisms governing the replication process. RNA viruses cannot penetrate plant cell walls unaided and must enter the cellular cytoplasm through mechanically induced wounds or assisted by a biological vector. After desencapsidation, their genome remains in the cytoplasm where it is translated, replicated and encapsidated in a coupled manner. Replication occurs in large viral replication complexes (VRCs), tethered to modified membranes of cellular organelles and composed by the viral RNA templates and by viral and host proteins. Cis‐acting elements located in viral RNA templates regulate the recognition by the virus‐encoded RNA‐dependent RNA polymerase and possibly contribute to VRC assembly and/or activation.

Key Concepts

The vast majority of plant RNA viruses have positive (mRNA sense) single‐stranded RNA genome.

Some plant RNA viruses have negative single‐stranded, or double‐stranded RNA genome.

Replication is at the core of the infection cycle of plant RNA viruses and occurs solely through RNA intermediates of positive and negative polarities.

Replication of most plant RNA viruses takes place in viral replication complexes tethered to modified membranes of cytoplasmic organelles.

Viral replication complexes are dynamic and contain the viral RNA, viral replication proteins and proteins from the host.

A viral‐RNA‐dependent RNA polymerase is responsible for the synthesis of new genomic RNA using parental genome as template.

Viral proteins and co‐opted host factors orchestrate the targeting of the genomic RNA to the membranes where replication takes place; they also contribute to the remodelling of the membranes that are used as scaffolds for tethering the viral replication complexes.

In addition to the role of co‐opted host factors in controlling the biogenesis of replication organelles and the composition, assembly and/or activity of the viral replication complex, they can post‐translationally modify viral proteins to regulate replication.

Primary sequence and structure elements of viral RNAs regulate template selection, initiation of the synthesis of complementary RNA strands and the assembly and activation of viral replication complexes.
SWI
/
SNF
Chromatin Remodelling and Human Cancer
Authors: Reisman David , Thompson Kenneth , Marquez‐Vilendrer Stefanie , Lu Li
Published: July 2016

Brahma (BRM) and Brahma‐related gene 1 (BRG1) are two mutually exclusively catalytic subunits of the switch in mating type/sucrose nonfermenting complex. These two key anticancer proteins are frequently targeted and silenced during cancer development. The anticancer function of BRM can be abrogated when it becomes acetylated or when it is epigenetically silenced. Central to BRM silencing is the presence of two inherited insertional polymorphisms within the BRM promoter that are statistically linked to cancer risk. Both BRM acetylation and silencing can be reversed by a number of compound families and might be important to how flavonoids and NSAIDS inhibit cancer. While BRG1 is very frequently mutated in most human cancers, it is more commonly inactivated by aberrant splicing and by an AKT‐pathway‐mediated‐translation block. While BRG1 and BRM are tied to deoxyribonucleic acid repair, growth control, differentiation, development, as well as epithelial–mesenchymal transition and are estimated to regulate 4–8% of the human genome, the inactivation of either protein is only modestly tumourigenic. This occurs in part because BRG1 and BRM are functionally redundant, which blunts the tumourigenic effect when only one gene is aberrantly silenced. Further insights into the mechanisms that regulate these genes may lead to novel therapeutic strategies that may reverse the silencing of these two important anticancer genes.

Key Concepts

Reversal of the epigenetic silencing of a gene may serve as a basis for drug therapy.

Anticancer genes are epigenetically regulated by insertional polymorphisms.

The functional redundancy of BRG1 and BRM thwarts cancer development.

Post‐translational modification of BRM and BRG1 alters the cellular roles of these proteins from growth inhibitors to growth promoters.

The loss of cofactors (i.e. BRG1 and/or BRM) for RB‐mediated‐growth inhibition could preclude the function of CDK inhibitors used clinically.

Specific SWI/SNF subunits are commonly mutated and inactivated in specific cancer types.

Diminished SWI/SNF activity, but not the complete abrogation of function, is tumourigenic.