bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside
Authors: Gregory Kyle S. , Liu Sai Man , Acharya K. Ravi 
Published: January 2020

Botulinum neurotoxins (BoNTs) are one of the most toxic proteins known to humans. Their molecular structure is comprised of three essential domains—a cell binding domain (HC), translocation domain and catalytic domain (light chain) . The HC domain facilitates the highly specific binding of BoNTs to the neuronal membrane via a dual‐receptor complex involving a protein receptor and a ganglioside. Variation in activity/toxicity across subtypes of serotype A has been attributed to changes in protein and ganglioside interactions, and their implications are important in the design of novel BoNT‐based therapeutics. Here, we present the structure of BoNT/A3 cell binding domain (HC/A3) in complex with the ganglioside GD1a at 1.75 Å resolution. The structure revealed that six residues interact with the three outermost monosaccharides of GD1a through several key hydrogen bonding interactions. A detailed comparison of structures of HC/A3 with HC/A1 revealed subtle conformational differences at the ganglioside binding site upon carbohydrate binding.
Sister Chromatid Cohesion, Chromosome Instability (CIN) and Diseases
Authors: Zhang Wei , Yuen Karen Wing Yee 
Published: January 2020

AbstractTo pass on the complete set of genetic information from mother to daughter cells in mitosis, or from parental germ cells to gametes in meiosis, chromosomal deoxyribonucleic acid (DNA) must be accurately replicated and sister chromatids must be held together before they separate in anaphase. Sister chromatid cohesion is a dynamic process that is regulated by the cohesin complex, cell cycle regulation of cohesin ring loading, cohesion establishment, maintenance and dissolution. Cohesion‐related proteins also play additional roles in DNA replication, DNA repair, and gene regulation. Defects in sister chromatid cohesion or cohesion dissolution will lead to aneuploidy and chromosome instability (CIN). Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing. Understanding of the pathology of these diseases enables recent development of cohesion genes as biomarkers in prognosis and therapies that target cohesion defects or CIN.Key ConceptsSister chromatid cohesion is an important cell cycle‐regulated process that maintains chromosome stability.Sister chromatid cohesion is established in S phase coupled with DNA replication, maintained in G2/M phase until anaphase onset.Many cohesion‐related proteins also play roles in DNA replication, DNA repair and gene regulation.Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing.Cohesion genes can be used as biomarkers in cancer prognosis, and cancer therapies can target tumours with cohesion defects or CIN.
Cryptochromes: How Blue Light Perception Influences Plant Physiology
Authors: Fantini Elio , Facella Paolo 
Published: January 2020

Abstract

Light plays a pivotal role in several physiological processes during plant growth, development and adaptation. Plants sense and respond to fluctuating light conditions using various photoreceptors such as phytochromes, cryptochromes and phototropins. In particular, cryptochromes are able to monitor, capture and transmit the stimuli of UVA/blue light in order to promote photomorphogenesis and regulate many aspects of plant development and growth including seed germination and seedling de‐etiolation, flowering induction, circadian rhythms and stress responses. Cryptochromes influence all these processes by modulating the expression pattern of several genes; such massive regulation is fundamental for optimising all physiological properties of plants throughout their life cycle.

Key Concepts

Light is essential for plant life.

Plants use photoreceptors to sense and monitor quality, direction, intensity and length of light stimulus.

Cryptochromes play fundamental roles in plant development.

Cryptochromes are highly conserved among plant species.

Cryptochromes regulate many light‐dependent physiological processes.
B‐Cell Antigen Receptor: Assembly and Diversification
Authors: Mohammad Mahwish M , Guillou Morwenna Le , Ghamlouch Hussein , Aoufouchi Said 
Published: January 2020

AbstractImmunoglobulin (Ig) genes of mammalian B cells undergo two processes that diversify their genomic sequence and structure. The first one concerns the BCR assembly that is achieved through a combinatorial rearrangement of a large number of V, D and J gene segments. This process is essential for B‐cell development and occurs during early B‐cell differentiation in the bone marrow without antigenic challenge. The second process includes somatic hypermutation (SHM), and class switch recombination (CSR), start when the B cell encounters an antigen at the periphery. While the two processes share the action of ubiquitous DNA repair factors to carry out all the steps necessary for creating recombination and mutations in genomic DNA, they are initiated by different lymphoid‐specific factors. On one hand, the action of recombination activating genes 1 and 2 (RAG1 and RAG2) is required for the V(D) J rearrangements and, on the other hand, the action of activation‐induced cytidine deaminase (AID) for both SHM and CSR. The ultimate goal of these diversification mechanisms is to create a dynamic and robust immune response.Key ConceptsV(D)J recombination is a programmed that generates B‐ and T‐cell receptors in vertebrates (BCR and TCR).V(D)J recombination requires precise cutting of the DNA at recombination signal sequences (RSS) followed by rejoining of the resulting termini. Imprecisions during the ends‐joining reaction contribute significantly to increasing the variability of the resulting functional BCR and TCR.RAG1, RAG2 and TdT are the three lymphoid‐specific factors needed for V(D)J recombination and for the junctional diversity observed during lymphoid development.B‐cells provide the antibody‐mediated immune response (humoral immunity). It can generate antibodies to an immense variety of pathogenic antigens.Somatic hypermutation (SHM) and class switch recombination (CSR) occur only in germinal centre B cells.During SHM, DNA repair mechanisms are diverted from their canonical role in preserving genomic integrity to permit high rate of mutations.SHM and CSR both occur in germinal centre in secondary lymphoid tissues and require activation‐induced cytidine deaminase (AID).AID deaminates deoxy‐cytosine on single‐stranded DNA.Ten–eleven translocation (TET) proteins (mainly TET2et TET3) are key regulators of immunoglobulin light chain rearrangement, class switch recombination and plasma cell differentiation.
Clinical Utility of Molecular Genetic Cancer Profiling
Authors: Joseph Loren 
Published: January 2020

Abstract

The ability to sequence entire genomes and transcriptomes is revolutionising cancer biology and, more slowly, cancer medicine. The evidence that large‐scale sequencing has clinical utility, that it improves outcomes, is slowly accumulating. A major controversy has centred on whether or not all tumours refractory to standard therapy should undergo therapy selection by molecular genetic cancer profiling (MGCP). Despite several completed or ongoing clinical trials, this issue is not settled; however, other forces now ensure that MGCP will become a routine diagnostic tool. Biopsies are becoming smaller, providing greater safety for patients, but yielding less DNA/RNA while there are now sufficiently many molecularly targeted agents approved in major cancers that testing by single‐gene assays is no longer practical or economical.

Key Concepts

A clinical test does not have inherent clinical utility.

The clinical utility of molecule genetic cancer profiling varies with the intended clinical use: diagnosis, prognosis, treatment selection, and cancer risk assessment.

Assessment of clinical utility does NOT include consideration of cost.

There is incomplete consensus on which genes should be in a molecular genetic cancer profile but in practice panels cover at most several hundred genes (ie much smaller than an exome).

Most molecular genetic cancer profiling has used tumor genomic DNA but assays are increasingly including analysis of RNA for translocation detection and gene expression.

The traditional method for determining clinical utility, the randomized clinical trial, is evolving to facilitate screening of many genes and many molecularly targeted agents rapidly.

Large‐scale clinical trials are underway to assess the clinical utility of applying molecular genetic panels to all cancers in a histology‐agnostic fashion.

Clinical trials for molecularly targeted agents predicted to be beneficial by molecular genetic cancer profiling are always conducted on patients with advanced disease who have already failed several established ‘lines of therapy’.

Likelihood of response to a new class of therapy, immune checkpoint inhibitors, might be predicted by microsatellite instability and, possibly, by the Tumor Mutation Burden.

Response to another new class of therapy, CAR‐T cells, might be mutation agnostic.
Emerging Role of Adrenomedullin as Sepsis Prognostic Marker
Authors: Lia Maria Stella , Angeletti Silvia , Bernardini Sergio , Minieri Marilena 
Published: January 2020

Abstract

Sepsis represents an important and global health problem. It affects 27–30 million people every year, 7–9 million of these die. Sepsis occurs when the body uncontrolled response to an infection injures its own tissues and organs. If it is not quickly recognised and treated, it may led to septic shock, multiorgan failure and death. Together with clinical signs, a series of biomarkers can be very useful in the early diagnosis of sepsis. Adrenomedullin (ADM) is one of these biomarkers, not only important for sepsis diagnosis but also particularly useful for prognosis. ADM is a hormone secreted by endothelial cells, involved in regulation of the endothelium barrier and vascular tone, so playing a decisive role in the inflammation process. The mid regional‐proadrenomedullin (MR‐proADM) is the molecule detected in septic patients because it is more stable than ADM and is released in an equimolar ratio of the active portion. MR‐proADM is capable to identify disease severity and progression, more accurately than other biomarkers and clinical scores. Inclusion of MR‐proADM assay in clinical routine could help the clinicians to manage septic patients especially by identifying their mortality risk.

Key Concepts

Sepsis is considered one of the most important public health concern with high rates of morbidity, mortality and resource consuming worldwide;

Sepsis is defined as uncontrolled immune response against infections;

A fast diagnosis of sepsis is necessary to promptly initiate the appropriate treatment;

Several biomarkers are adopted in clinical settings for sepsis diagnosis and prognosis, but the ‘gold standard’ has not found yet;

Mid Regional‐proAdrenomedullin (MR‐proADM) is a novel promising biomarker of prognosis associated to sepsis severity playing an important role in the initial evaluation and clinical management of septic patient.
Ramularia collo‐cygni
– An Enemy in Waiting
Authors: Dussart Francois , Creissen Henry E , Havis Neil D 
Published: January 2020

Abstract

Ramularia collo‐cygni
, the agent responsible for Ramularia leaf spot disease of barley, possesses many mechanisms for avoiding detection by the host, which enables it to survive as an endophyte for much of the plant's life cycle before eventually turning pathogenic. The fungus has also eluded farmers and scientists for decades as it is a late season disease that often displays symptoms after the last possible fungicide intervention when crop scouting for disease has been completed. Visual symptoms are also hard to distinguish from other pathogens, which has resulted in misdiagnoses. The ability of the fungus to spread not only via infected seed but also on infected straw and wind dispersal, coupled with its ability to rapidly evolve resistance to fungicides, has resulted in an escalation in the perceived threat it presents to barley production worldwide. A greater understanding of the plant–fungus interaction is required if future control strategies are to be successful.

Key Concepts

Plant–fungi interactions can be complex and highly variable, including mutualism, parasitism and commensalism.

Global movement of seed can significantly influence the spread of seed‐borne diseases.

Plant breeding for disease control requires identification of a suitable breeding target, which may be challenging.

Breeding for resistance to one pathogen may lead to control issues for another pathogen.

Integrated pest management practices must consider nonchemical control measures and, when using pesticides, antiresistance strategies.

Single‐site fungicides are vulnerable to losses in efficacy due to the evolution of resistance in the pathogen population.
A Highly Stretchable, Real‐Time Self‐Healable Hydrogel Adhesive Matrix for Tissue Patches and Flexible Electronics
Authors: Luo Jun , Yang Jiaojiao , Zheng Xiaoran , Ke Xiang , Chen Yantao , Tan Hong , Li Jianshu 
Published: January 2020

AbstractThe development of biocompatible self‐healable hydrogel adhesives for skin or wet, stretchable surfaces in air or under water is highly desirable for various biomedical applications ranging from skin patches to bioelectronics. However, it has been proven to be very challenging because most existing hydrogel adhesives are cytotoxic, or poorly adhere to dynamic or stretchable surfaces in wet environments. In this study, multifunctional hydrogel adhesives derived from silk fibroin (SF) and tannic acid (TA) are effectively constructed with high extensibility (i.e., up to 32 000%), real‐time self‐healing capability, underwater adhesivity, water‐sealing ability, biocompatibility, and antibiotic properties. According to all‐atom molecular dynamics simulation studies, the properties of the hydrogel adhesives, especially high extensibility, are mainly attributed to the hydrogen bonds between TA and the SF chains in water, and water and TA molecules can result in loose assemblies with fewer β‐sheets, and more random coils in the SF. Conductivity can also be easily introduced to the adhesive matrix and adjusted when the strain of the adhesives occurs. Considering that it has multiple functions and can be efficiently prepared, the proposed hydrogel adhesives have the potential for future medical applications, such as tissue adhesives and integrated bioelectronics.
Recent Advances in the Transdermal Delivery of Protein Therapeutics with a Combinatorial System of Chemical Adjuvants and Physical Penetration Enhancements
Authors: An Young‐Hyeon , Park Mihn Jeong , Lee Joon , Ko Junghyeon , Kim Su‐Hwan , Kang Dong Hyeon , Hwang Nathaniel S. 
Published: January 2020

AbstractSince the development of protein‐based therapeutics, research has been underway to deliver protein therapeutics into the systemic circulation and target sites have been actively conducted. Most protein‐based therapeutics require parenteral administration, due to their intrinsic vulnerability and susceptibility to enzyme‐mediated degradation. Among the routes of administration, the transdermal delivery system has been regarded as a promising technique to deliver protein therapeutics, offering the advantages of painless administration, ease of termination, and avoidance of first‐pass metabolism. However, unlike small molecular drugs, protein therapeutics have limited skin penetration, due to their macromolecular and hydrophilic properties. Both cheimcal adjuvants (CAs)‐treatment methods and physical penetration enhancer methods (PPEs) have been utilized to increase skin permeability for protein therapeutics. The CAs, which include chemical penetration enhancers and nanocarriers, permit the protein therapeutics to transport easily into the skin, by modifying the stratum corneum (SC) or fabricating their stable formulation. The PPEs, including iontophoresis, electroporation, and ultrasound, can improve the skin permeability of the therapeutic agent through disrupting the SC. In this review, the techniques of both chemical and physical enhancement methods are introduced and an overview of the latest approaches to the transdermal delivery of protein therapeutics is provided.
Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment
Authors: Peng Yang , Bariwal Jitender , Kumar Virender , Tan Chalet , Mahato Ram I. 
Published: January 2020

AbstractNanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.
Extreme soil surface temperatures reflect need to rethink agronomic management
Authors: O'Brien Peter L. , Hatfield Jerry L. 
Published: January 2020

AbstractThe soil surface exists at the soil–atmosphere interface and is critical in regulating transfers of water, energy, and nutrients in agroecosystems. Soil surface temperature plays an important role in the rate and quantity at which these resources cross the interface, as temperature regulates numerous physical, chemical, and biological processes. Many current management practices manipulate soil surface temperatures, especially through tillage or residue management, to create conditions suitable for early‐season crop growth. However, these conditions persist beyond plant establishment and have the potential to develop extremely high temperatures, even in historically mild climates. We show the potential for extreme maximum soil surface temperatures in Iowa after crop establishment but before canopy closure and discuss possible consequences of those temperatures. Given the conditions required to develop extreme maximum temperatures, we contend that soil surface temperatures may be an indicator of conditions that are inconsistent with highly productive, sustainable, efficient agroecosystems.
Doping High‐Mobility Donor–Acceptor Copolymer Semiconductors with an Organic Salt for High‐Performance Thermoelectric Materials
Authors: Guo Jing , Li Guodong , Reith Heiko , Jiang Lang , Wang Ming , Li Yuhao , Wang Xinhao , Zeng Zebing , Zhao Huaizhou , Lu Xinhui , Schierning Gabi , Nielsch Kornelius , Liao Lei , Hu Yuanyuan 
Published: January 2020

AbstractOrganic semiconductors (OSCs) are attractive for fabrication of thermoelectric devices with low cost, large area, low toxicity, and high flexibility. In order to achieve high‐performance organic thermoelectric devices (OTEs), it is essential to develop OSCs with high conductivity (σ ), large Seebeck coefficient (S), and low thermal conductivity (κ ). It is equally important to explore efficient dopants matching the need of thermoelectric devices. The thermoelectric performance of a high‐mobility donor–acceptor (D–A) polymer semiconductor, which is doped by an organic salt, is studied. Both a high p‐type electrical conductivity approaching 4 S cm−1 and an excellent power factor (PF) of 7 µW K−2 m−1 are obtained, which are among the highest reported values for polymer semiconductors. Temperature‐dependent conductivity, Seebeck coefficient and power factor of the doped materials are systematically investigated. Detailed analysis on the results of thermoelectric measurements has revealed a hopping transport in the materials, which verifies the empirical relationship: S ∝ σ−1/4 and PF ∝ σ1/2. The results demonstrate that D–A copolymer semiconductors with proper combination of dopants have great potential for fabricating high‐performance thermoelectric devices.
The impact of tillage row orientation on physical and chemical sediment enrichment
Authors: Wacha Kenneth M. , Papanicolaou A. N. Thanos , Abban Benjamin K. , Wilson Christopher G. , Giannopoulos Christos P. , Hou Tingyu , Filley Timothy R. , Hatfield Jerry L. 
Published: January 2020

AbstractThis study aimed to better understand how tillage row orientation with respect to dominant flow‐pathway along hillslope impacts runoff and the transport of different sediment size fractions. Experimental plots were constructed in contour ridge till (CRT) and parallel ridge till (PRT) sites to monitor runoff and sediment fluxes. Particle size fractions of the sediment, along with organic C and N contents were measured to quantify physical and chemical enrichment ratios for the two tillage orientations. In the CRT plot, tillage produced large oriented roughness elements along the contours, which acted as little check dams, while in the PRT site, the roughness elements helped confine and concentrate the runoff. In the CRT, the “check dams” resulted in a runoff coefficient of .03, while in the PRT, the flow confinement between rows produced a runoff coefficient of .82. Moreover, the erosion rates at the CRT site were 97% less than those in the PRT plot. Large contours produced finer sediment fractions due to the selective sorting in ponded furrows. More aggregate sediment fractions were present in the PRT site, which was dominated by rill erosion. Physical enrichment revealed selective entrainment of finer sediment particles during erosion. Finer‐grain particles with higher specific surface areas, attached more organic C resulting in chemical enrichment. Physical and chemical enrichment methods were found to be in good agreement. These findings suggest transport models that can simulate size fraction updates to the soil active layer can be used to estimate SOC redistribution and hence more accurate C budgets.
The sorghum epicuticular wax locus Bloomless2 reduces plant damage in P898012 caused by the sugarcane aphid
Authors: Harris‐Shultz Karen , Punnuri Somashekhar , Knoll Joseph E. , Ni Xinzhi , Wang Hongliang 
Published: January 2020

AbstractThe sugarcane aphid [Melanaphis sacchari] has been rapidly spreading in the southern United States with devastating impacts on sorghum [Sorghum bicolor (L.) Moench]. Previous studies have shown the sorghum epicuticular wax mutants, in particular a bloomless2 (bm2) mutant and a sparse bloom mutant, were resistant to greenbugs [Schizaphis graminum], a type of aphid. In this study we sought to determine if five different genotypes, which all have mutations in the Bm2 locus, differ for sugarcane aphid resistance as compared to their respective wild‐type plants (P954035, P898012, and Tx7078). Two greenhouse studies with artificial infestation and one field study under natural infestation were conducted. Aphid numbers on the second leaf from the top and the lowest green leaf, plant damage, and plant growth stage were assessed at weekly intervals. The Greenhouse Test 2 and the Field test were the most effective at determining plant resistance and susceptibility to the sugarcane aphid. Bm2 mutants in the P898012 background had greater aphid damage than their wild type plants. These findings suggest that the Bm2 locus has a role in reducing aphid damage in the P898012 background yet has a limited role in the Tx7078 and P954035 backgrounds.