bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation mechanism of DEA as an activator on aqueous MEA solution for postcombustion CO2 capture
Authors: Liu Helei , Li Moxia , Luo Xiao , Liang Zhiwu , Idem Raphael , Tontiwachwuthikul Paitoon
Published: March 2018

In this work, Diethanolamine (DEA) was considered as an activator to enhance the CO2 capture performance of Monoethanolamine (MEA). The addition of DEA into MEA system was expected to improve disadvantages of MEA on regeneration heat, degradation, and corrosivity. To understand the reaction mechanism of blended MEA‐DEA solvent and CO2, 13C nuclear magnetic resonance (NMR) technique was used to study the ions (MEACOO‐, DEACOO–, MEA, DEA, MEAH+, DEAH+,
,
) speciation in the blended MEA‐DEA‐CO2‐H2O systems with CO2 loading range from 0 to 0.7 mol CO2/mol amine at the temperature of 301 K. The different ratios of MEA and DEA (MEA: DEA = 2.0:0, 1.5:0.5, 1.0:1.0, and 0:2.0) were studied to comprehensively investigate the role of DEA in the system of MEA‐DEA‐CO2‐H2O. The results revealed that DEA performs the coordinative role at the low CO2 loading and the competitive role at high CO2 loading. Additionally, the mechanism was also proposed to interpret the reaction process of the blended solvent with CO2. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2515–2525, 2018
Brassicales phylogeny inferred from 72 plastid genes: A reanalysis of the phylogenetic localization of two paleopolyploid events and origin of novel chemical defenses
Authors: Edger Patrick P. , Hall Jocelyn C. , Harkess Alex , Tang Michelle , Coombs Jill , Mohammadin Setareh , Schranz M. Eric , Xiong Zhiyong , Leebens‐Mack James , Meyers Blake C. , Sytsma Kenneth J. , Koch Marcus A. , Al‐Shehbaz Ihsan A. , Pires J. Chris
Published: March 2018

PREMISE OF THE STUDY

Previous phylogenetic studies employing molecular markers have yielded various insights into the evolutionary history across Brassicales, but many relationships between families remain poorly supported or unresolved. A recent phylotranscriptomic approach utilizing 1155 nuclear markers obtained robust estimates for relationships among 14 of 17 families. Here we report a complete family‐level phylogeny estimated using the plastid genome.

METHODS

We conducted phylogenetic analyses on a concatenated data set comprising 44,926 bp from 72 plastid genes for species distributed across all 17 families. Our analysis includes three additional families, Tovariaceae, Salvadoraceae, and Setchellanthaceae, that were omitted in the previous phylotranscriptomic study.

KEY RESULTS

Our phylogenetic analyses obtained fully resolved and strongly supported estimates for all nodes across Brassicales. Importantly, these findings are congruent with the topology reported in the phylotranscriptomic study. This consistency suggests that future studies could utilize plastid genomes as markers for resolving relationships within some notoriously difficult clades across Brassicales. We used this new phylogenetic framework to verify the placement of the At‐α event near the origin of Brassicaceae, with median date estimates of 31.8 to 42.8 million years ago and restrict the At‐β event to one of two nodes with median date estimates between 85 to 92.2 million years ago. These events ultimately gave rise to novel chemical defenses and are associated with subsequent shifts in net diversification rates.

CONCLUSIONS

We anticipate that these findings will aid future comparative evolutionary studies across Brassicales, including selecting candidates for whole‐genome sequencing projects.
Cyclophosphamide versus etoposide in combination with total body irradiation as conditioning regimen for adult patients with Ph‐negative acute lymphoblastic leukemia undergoing allogeneic stem cell transplant: On behalf of the ALWP of the European Society for Blood and Marrow Transplantation
Authors: Czyz Anna , Labopin Myriam , Giebel Sebastian , Socié Gerard , Apperley Jane , Volin Liisa , Reményi Péter , Yakoub‐Agha Ibrahim , Orchard Kim , Michallet Mauricette , Stuhler Gernot , Chaganti Sridhar , Murray Martin , Aljurf Mahmoud , Bloor Adrian , Passweg Jacob , Finke Jürgen , Mohty Mohamad , Nagler Arnon
Published: March 2018

Allogeneic hematopoietic cell transplantation (alloHCT) with myeloablative conditioning based on total body irradiation (TBI) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vp/TBI). The goal of this study was to retrospectively compare these two regimens. Adult patients with Ph‐negative ALL treated with alloHCT in first or second complete remission who received Cy/TBI (n = 1346) or Vp/TBI (n = 152) conditioning were included in the analysis. In a univariate analysis, as compared to Cy/TBI, the use of Vp/TBI was associated with reduced incidence of relapse (17% vs. 30% at 5 years, P = .007), increased rate of leukemia‐free survival (60% vs. 50%, P = .04), and improved “graft versus host disease (GVHD) and relapse‐free survival” (GRFS, 43% vs. 33%, P = .04). No significant effect could be observed in terms of the incidence of nonrelapse mortality or acute or chronic GVHD. In a multivariate model, the use of Vp/TBI was associated with reduced risk of relapse (HR = 0.62, P = .04) while the effect on other study end‐points was not significant. In conclusion, conditioning regimen based on Vp combined with TBI appears more effective for disease control than the combination of Cy with TBI for adult patients with Ph‐negative ALL treated with alloHCT.
Transitioning patients with immune thrombocytopenia to second‐line therapy: Challenges and best practices
Authors: Cuker Adam
Published: March 2018

In patients with immune thrombocytopenia who do not adequately respond to first‐line therapy, there is no clear consensus on which second‐line therapy to initiate and when. This situation leads to suboptimal approaches, including prolonged exposure to treatments that are not intended for long‐term use (eg, corticosteroids) and overuse of off‐label therapies (eg, rituximab) while approved, more efficacious options exist. These approaches may not only fail to address symptoms and burden of disease, but may also worsen health‐related quality of life. A better understanding of available second‐line treatments may ensure best use of therapeutic options and thereby optimize patient outcomes.
Sex‐specific functional adaptation of the femoral diaphysis to body composition
Authors: Lacoste Jeanson Alizé , Santos Frédéric , Dupej Ján , Velemínská Jana , Brůžek Jaroslav
Published: March 2018

Objectives

The human femoral diaphysis is often used to reconstruct loading histories (mobility, activity, body mass). The proximal femur is known to be differentially affected by changes in total fat‐mass (FM), fat‐free mass (FFM), and body fat percentage (BF%), but the adaptation of the entire diaphysis to body composition has not been thoroughly characterized to date. Understanding how the femoral diaphysis adapts to body components would benefit biomechanical interpretations of the femoral variation and nutrition‐related studies.

Methods

Combining various methods from clinical nutrition, biological anthropology, and geometric morphometrics, we evaluated the correlation of measures taken on the entire femoral diaphysis with estimated FM, FFM, and BF% from 61 CT scans (17 females, 44 males). The sample was predominantly composed of people with obesity.

Results

Cortical area of the cross‐sections and local cortical thickness showed high correlation with BF% in particular, in females only. The curvature significantly decreased with FM and BF% in both sexes. The lowest correlations are found with FFM.

Conclusions

The observed sexual dimorphism is consistent with differing aging processes; cortical bone decreases in females through endosteal resorption while it remains almost constant in males who compensate for endosteal resorption by periosteal apposition on the diaphyseal surface. The functional adaptation to compressive forces indicates a systemic endosteal apposition of bone material with increased BF% and FM in females only. FM and BF% are linked to a straighter femur in both sexes, suggesting an optimization of the resistance to compressive loads by distributing them more linearly along the entire diaphysis.
Parental posttraumatic stress and child behavioral problems in world trade center responders
Authors: Uchida Mai , Feng Huifen , Feder Adriana , Mota Natalie , Schechter Clyde B. , Woodworth Hilary D. , Kelberman Caroline G. , Crane Michael , Landrigan Philip , Moline Jacqueline , Udasin Iris , Harrison Denise , Luft Benjamin J. , Katz Craig , Southwick Steven M. , Pietrzak Robert H.
Published: March 2018

Background

We investigated trans‐generational associations between Post Traumatic Stress Disorder (PTSD) symptoms in World Trade Center (WTC) responders and behavioral problems in their children.

Methods

Participants were WTC responders—8034 police and 8352 non‐traditional (eg, construction workers)—with one or more children at the time of their first visit to the World Trade Center Health Program (WTC‐HP). Self‐report questionnaires were administered approximately 4 years after the 9/11 WTC attack.

Results

A total of 31.4% of non‐traditional and 20.0% of police responders reported behavioral problems in their children. Non‐traditional responder status, female sex, Hispanic ethnicity, more life stressors, more WTC‐related PTSD symptoms, and dysphoric arousal symptoms were significant correlates of behavioral problems in responders’ children.

Conclusions

Specific parental sociodemographic, psychosocial and clinical characteristics, as well as PTSD symptom severity, were significant correlates of child behavior problems. Findings encourage monitoring and early intervention for children of disaster responders, particularly those at highest risk.
Codability of industry and occupation information from cancer registry records: Differences by patient demographics, casefinding source, payor, and cancer type
Authors: Silver Sharon R. , Tsai Rebecca J. , Morris Cyllene R. , Boiano James M. , Ju Jun , Scocozza Marilyn S. , Calvert Geoffrey M.
Published: March 2018

Introduction

Industry and occupation (I&O) information collected by cancer registries is useful for assessing associations among jobs and malignancies. However, systematic differences in I&O availability can bias findings.

Methods

Codability by patient demographics, payor, identifying (casefinding) source, and cancer site was assessed using I&O text from first primaries diagnosed 2011‐2012 and reported to California Cancer Registry. I&O were coded to a U.S. Census code or classified as blank/inadequate/unknown, retired, or not working for pay.

Results

Industry was codable for 37% of cases; 50% had “unknown” and 9% “retired” instead of usual industry. Cases initially reported by hospitals, covered by preferred providers, or with known occupational etiology had highest codable industry; cases from private pathology laboratories, with Medicaid, or diagnosed in outpatient settings had least. Occupation results were similar.

Conclusions

Recording usual I&O for retirees and improving linkages for reporting entities without patient access would improve I&O codability and research validity.
Risk factors associated with allergic sensitization and asthma phenotypes among poultry farm workers
Authors: Ngajilo Dorothy , Singh Tanusha , Ratshikhopha Edith , Dayal Payal , Matuka Onnicah , Baatjies Roslynn , Jeebhay Mohamed F.
Published: March 2018

Background

This study investigated the risk factors for occupational allergic sensitization and various asthma phenotypes in poultry‐workers.

Methods

A cross‐sectional study of 230 workers used a modified ECRHS questionnaire, spirometry, FeNO, Phadiatop, and sIgE to poultry farming related allergens.

Results

Worker's mean age was 37 ± 9 years, 68% male, 43% current‐smokers, 34% atopic, and 5% casual‐workers. The prevalence of non‐atopic asthma (NAA = 7%) was higher than atopic‐asthma (AA = 5%) and probable allergic occupational‐asthma (OA = 3%). Sensitization to at least one poultry farming related allergen was 24%. Workers sensitized to chicken‐specific‐allergens were more likely to be atopic (ORunadj = 20.9, 95%CI: 4.7‐93.2) or employed as casual‐workers (ORunadj = 6.0, 95%CI: 1.1‐35.9). Work‐related chest symptoms were associated the rearing‐department (ORadj = 3.2, 95%CI: 1.2‐8.4) and exposure to high gas/dust/fumes (ORadj = 4.8, 95%CI: 2.4‐9.5). Airflow reversibility (ORadj = 10.9, 95%CI: 2.0‐60.3) was significantly associated with casual‐work status.

Conclusion

Allergic and non‐allergic mechanisms play a role in asthma development among poultry‐workers with casual workers demonstrating increased risk.
Clinical and laboratory factors contributing to uninterpretable beryllium lymphocyte proliferation tests (BeLPT)
Authors: Smith Derek E. , Golden Ashley P. , Stange Arthur W. , Barker Elizabeth , Mroz Margaret , Barón Anna E. , Ghosh Debashis , Maier Lisa , Cragle Donna , Newman Lee S.
Published: March 2018

Background

The beryllium lymphocyte proliferation test (BeLPT), has become the principal clinical test for detecting beryllium sensitization and chronic beryllium disease. Uninterpretable BeLPT results can occur in a small but significant proportion of tests from poor lymphocyte growth (PG) or over proliferation of lymphocytes (OP). The clinical and laboratory causes of uninterpretable results are not known.

Methods

BeLPT data from the US Department of Energy‐supported Former Worker Screening Program were analyzed for a 10‐year period. Drivers of uninterpretable BeLPTs were investigated using multivariable models and classification techniques.

Results

Three participant attributes were significantly associated with PG, while OP showed no significant associations. Serum lot for the lymphocyte growth medium accounted for 21% of the variation in PG and 16% in OP.

Conclusion

Serum lots influence the likelihood of having uninterpretable BeLPT. To better understand uninterpretable results and possibly reduce their occurrence, additional laboratory‐related factors should be addressed.
Clinical, biochemical, and genetic features of four patients with short‐chain enoyl‐CoA hydratase (ECHS1) deficiency
Authors: Fitzsimons Patricia E. , Alston Charlotte L. , Bonnen Penelope E. , Hughes Joanne , Crushell Ellen , Geraghty Michael T. , Tetreault Martine , O'Reilly Peter , Twomey Eilish , Sheikh Yusra , Walsh Richard , Waterham Hans R. , Ferdinandusse Sacha , Wanders Ronald J. A. , Taylor Robert W. , Pitt James J. , Mayne Philip D.
Published: March 2018

Short‐chain enoyl‐CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292). Clinical presentation includes infantile‐onset severe developmental delay, regression, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). Characteristic abnormal biochemical findings are secondary to dysfunction of valine metabolism. We describe four patients from two consanguineous families (one Pakistani and one Irish Traveler), who presented in infancy with LS. Urine organic acid analysis by GC/MS showed increased levels of erythro‐2,3‐dihydroxy‐2‐methylbutyrate and 3‐methylglutaconate (3‐MGC). Increased urine excretion of methacrylyl‐CoA and acryloyl‐CoA related metabolites analyzed by LC‐MS/MS, were suggestive of SCEH deficiency; this was confirmed in patient fibroblasts. Both families were shown to harbor homozygous pathogenic variants in the ECHS1 gene; a c.476A > G (p.Gln159Arg) ECHS1variant in the Pakistani family and a c.538A > G, p.(Thr180Ala) ECHS1 variant in the Irish Traveler family. The c.538A > G, p.(Thr180Ala) ECHS1 variant was postulated to represent a Canadian founder mutation, but we present SNP genotyping data to support Irish ancestry of this variant with a haplotype common to the previously reported Canadian patients and our Irish Traveler family. The presence of detectable erythro‐2,3‐dihydroxy‐2‐methylbutyrate is a nonspecific marker on urine organic acid analysis but this finding, together with increased excretion of 3‐MGC, elevated plasma lactate, and normal acylcarnitine profile in patients with a Leigh‐like presentation should prompt consideration of a diagnosis of SCEH deficiency and genetic analysis of ECHS1. ECHS1 deficiency can be added to the list of conditions with 3‐MGA.
The psychosocial impact of 22q11 deletion syndrome on patients and families: A systematic review
Authors: Vo Oanh Kieu , McNeill Alisdair , Vogt Katharina Sophie
Published: March 2018

The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders in humans, affecting around 1:2,000 to 1: 4,000 people. 22q11DS affects multiple body systems and is associated with multiple physical problems. Given the high rate of physical morbidity associated with the 22q11DS, it was hypothesized that it would exert a high psychosocial impact on patients and their relatives. To investigate this, a systematic review of the literature and narrative synthesis was performed. Three major themes emerged. First, the complex and conflicting emotions experienced by family members resulting from the diagnosis. Second, the pervasive educational and health‐care challenges associated with the diagnosis and third that people affect by 22q11DS strived for individualism. The results of this review help to inform clinical management of families with 22q11DS.
Genetic counseling among minority populations in the era of precision medicine
Authors: Halbert Chanita H. , Harrison Barbara W.
Published: March 2018

Precision medicine includes the use of genetic variation to determine the prevention, pathology, management, and treatment of disease, which has the potential to significantly change the practice of healthcare. As such, its success depends on (a) having reliable information about the effects of genetic variation on disease processes; and (b) the patient's understanding of their own genetic makeup such that they can use that information to affect their lifestyle and diet. Given the history of low engagement of under‐represented minority populations in both clinical genetic services and genetic research, both of these aspects will be challenged and must be addressed before the benefits of precision medicine will be fully realized. Reflecting on lessons learned in the field of cancer genetic counseling, we present key issues to consider as we look forward to providing genetic counseling to minority communities in the context of precision medicine.
Clinical genetic counselors: An asset in the era of precision medicine
Authors: Wicklund Catherine A. L. , Duquette Debra A. , Swanson Amy L.
Published: March 2018

Trying to predict what genetic counseling will look like in the era of precision medicine is a continuous challenge. According to the National Institutes of Health, precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. In order to explore the future of genetic counseling practice in this era, this article examines the current genetic counseling practice, internal and external forces that most likely will continue to shape the genetic counseling profession, and discusses the most important aspects of what genetic counselors have to offer in the era of precision medicine.
Genetic counseling globally: Where are we now?
Authors: Ormond Kelly E. , Laurino Mercy Ygoña , Barlow‐Stewart Kristine , Wessels Tina‐Marié , Macaulay Shelley , Austin Jehannine , Middleton Anna
Published: March 2018

The genetic counseling profession is continuing to develop globally, with countries in various stages of development. In some, the profession has been in existence for decades and is increasingly recognized as an important provider of allied health, while in others it is just beginning. In this article, we describe the current global landscape of the genetic counseling specialty field's professional development. Using examples of the United States, United Kingdom, Canada, Australia, South Africa, and various countries in Asia, we highlight the following: (a) status of genetic counseling training programs, (b) availability of credentialing through government and professional bodies (certification, registration, and licensure), and potential for international reciprocity, (c) scope of clinical practice, and (d) health‐care system disparities and cultural differences impacting on practice. The successful global implementation of precision medicine will require both an increased awareness of the importance of the profession of “genetic counselor” and flexibility in how genetic counselors are incorporated into each country's health‐care market. In turn, this will require more collaboration within and across nations, along with continuing engagement of existing genetic counseling professional societies.
Salicylate‐Directed C−O Bond Cleavage: Iron‐Catalyzed Allylic Substitution with Grignard Reagents
Authors: Ma Enlu , Jiang Yifan , Chen Yuanjin , Qi Longying , Yan Xiaoyu , Li Zhiping
Published: March 2018

Selective C−O bond cleavage is of high interest for modern organic synthesis. A strategy for selective allylic C−O bond cleavage using ethyl salicylate as a directing leaving group has been developed. The reaction is initiated by the chelation of the ortho‐ester phenolic group with iron catalyst. The π‐allyl iron intermediate is generated and reacts with Grignard reagents to give the allylic substitution products. The excellent selectivity of C−O bond cleavage is achieved in multiple allylic C−O bond‐containing substrates with the aid of the salicylate‐directed strategy.
Captive chimpanzee (Pan troglodytes) behavior as a function of space per animal and enclosure type
Authors: Neal Webb Sarah J. , Hau Jann , Schapiro Steven J.
Published: March 2018

Space per animal, or animal density, and enclosure type are important elements of functionally appropriate captive environments (FACEs) for chimpanzees. The National Institutes of Health (NIH) recommends that captive chimpanzees be maintained in areas of >250 ft2/animal. Several studies have investigated chimpanzee behavior in relation to space per animal, but only two studies have examined these variables while attempting to hold environmental complexity constant. Both have found few, if any, significant differences in behavior associated with increased space per animal. The NIH does not provide recommendations pertaining to enclosure type. Although Primadomes™ and corrals are considered acceptable FACE housing, no studies have investigated chimpanzee behavior in relation to these two common types of enclosures. We examined the NIH space per animal recommendation, and the effects of enclosure type, while maintaining similar levels of environmental complexity. We used focal animal observations to record the behavior of 22 chimpanzees in three social groups following within‐facility housing transfers. Chimpanzees that were moved from an area with space below the NIH recommendation to the same type of enclosure with space above the recommendation (dome to double dome) exhibited significantly more locomotion and behavioral diversity post‐transfer. Chimpanzees that were moved from an area with space below the recommendation to a different type of enclosure with space above the recommendation (dome to corral) exhibited significant increases in foraging and behavioral diversity, and a decrease in rough scratching. Lastly, chimpanzees that were moved from an area above the recommendation to a different enclosure type with space equal to the recommendation (corral to double dome) exhibited an increase in behavioral diversity. These results add to the body of literature that addresses the concept of specific minimum space requirements per chimpanzee, and highlight the need for more empirical investigation of the relationship between space per chimpanzee, behavior, and welfare.
Prevalence and characteristics of hair plucking in captive bonobos (Pan paniscus) in North American zoos
Authors: Brand Colin M. , Marchant Linda F.
Published: March 2018

When primates exhibit hair loss and are observed to engage in self or social hair plucking (a rapid jerking away of the hair shaft and follicle by the hand or mouth, often accompanied by inspection, and consumption) the altered appearance, and behavior patterns are thought to reflect individual physiological, and psychological well‐being. Hair loss and hair plucking occur in many captive primate species, including all of the great apes. We present the first survey of this behavior among captive bonobos (N = 88; 50 females and 38 males) in seven zoos in the United States. We found that 43% of the population engaged in this behavior pattern and discounting youngsters (who are not observed to hair pluck until the age of five), 58% of individuals hair plucked. Of the individuals who hair plucked, 97% engaged in social plucking, whereas 46% engaged in self‐directed plucking. We regressed the occurrence of hair plucking with multiple predictor variables using binary logistic regression and multimodel inference to determine which predictors best explained the prevalence of self‐directed and social plucking. We also analyzed publicly available data on hair plucking in captive chimpanzees. We found that the occurrence of another abnormal behavior, age, origin, and pelage condition best explained self‐directed plucking in bonobos. Social plucking was explained by age, origin, pelage, and sex. Our analysis of chimpanzee hair plucking revealed that plucking is strongly influenced by rearing and sex. This study demonstrates that hair plucking is more prevalent in captive bonobos compared to captive chimpanzees and gorillas, however, the covariates associated with hair plucking for each species are different. Our data suggest a potential link between self‐directed plucking and well‐being. However, the higher prevalence and etiology of social hair plucking is more difficult to explain.
Neurochemical abnormalities in premanifest and early spinocerebellar ataxias
Authors: Joers James M. , Deelchand Dinesh K. , Lyu Tianmeng , Emir Uzay E. , Hutter Diane , Gomez Christopher M. , Bushara Khalaf O. , Eberly Lynn E. , Öz Gülin
Published: March 2018

Objective

To investigate whether early neurochemical abnormalities are detectable by high‐field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without manifestation of ataxia.

Methods

A cohort of 100 subjects (N = 18–21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance‐weighted discrimination) was used to combine regional profiles into an “MRS score.”

Results

MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early‐manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6.

Interpretation

Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality‐of‐life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816–829
Evidence for the Role of Intracellular Water Lifetime as a Tumour Biomarker Obtained by In Vivo Field‐Cycling Relaxometry
Authors: Ruggiero Maria Rosaria , Baroni Simona , Pezzana Stefania , Ferrante Gianni , Geninatti Crich Simonetta , Aime Silvio
Published: March 2018

It was established through in vivo T1 measurements at low magnetic fields that tumour cells display proton T1 values that are markedly longer than those shown by healthy tissue. Moreover, it has been found that the elongation of T1 parallels the aggressiveness of the investigated tumour. The T1 lengthening is associated with an enhanced water exchange rate across the transcytolemmal membrane through an overexpression/upregulation of GLUT1 and Na+/K+ ATPase transporters. It follows that the intracellular water lifetime represents a hallmark of tumour cells that can be easily monitored by measuring T1 at different magnetic field strengths ranging from 0.2 to 200 mT.
Vesicle Tubulation with Self‐Assembling DNA Nanosprings
Authors: Grome Michael W. , Zhang Zhao , Pincet Frédéric , Lin Chenxiang
Published: March 2018

A major goal of nanotechnology and bioengineering is to build artificial nanomachines capable of generating specific membrane curvatures on demand. Inspired by natural membrane‐deforming proteins, we designed DNA‐origami curls that polymerize into nanosprings and show their efficacy in vesicle deformation. DNA‐coated membrane tubules emerge from spherical vesicles when DNA‐origami polymerization or high membrane‐surface coverage occurs. Unlike many previous methods, the DNA self‐assembly‐mediated membrane tubulation eliminates the need for detergents or top‐down manipulation. The DNA‐origami design and deformation conditions have substantial influence on the tubulation efficiency and tube morphology, underscoring the intricate interplay between lipid bilayers and vesicle‐deforming DNA structures.
Reversible Switching between Highly Porous and Nonporous Phases of an Interpenetrated Diamondoid Coordination Network That Exhibits Gate‐Opening at Methane Storage Pressures
Authors: Yang Qing‐Yuan , Lama Prem , Sen Susan , Lusi Matteo , Chen Kai‐Jie , Gao Wen‐Yang , Shivanna Mohana , Pham Tony , Hosono Nobuhiko , Kusaka Shinpei , Perry John J. , Ma Shengqian , Space Brian , Barbour Leonard J. , Kitagawa Susumu , Zaworotko Michael J.
Published: March 2018

Herein, we report that a new flexible coordination network, NiL2 (L=4‐(4‐pyridyl)‐biphenyl‐4‐carboxylic acid), with diamondoid topology switches between non‐porous (closed) and several porous (open) phases at specific CO2 and CH4 pressures. These phases are manifested by multi‐step low‐pressure isotherms for CO2 or a single‐step high‐pressure isotherm for CH4. The potential methane working capacity of NiL2 approaches that of compressed natural gas but at much lower pressures. The guest‐induced phase transitions of NiL2 were studied by single‐crystal XRD, in situ variable pressure powder XRD, synchrotron powder XRD, pressure‐gradient differential scanning calorimetry (P‐DSC), and molecular modeling. The detailed structural information provides insight into the extreme flexibility of NiL2. Specifically, the extended linker ligand, L, undergoes ligand contortion and interactions between interpenetrated networks or sorbate–sorbent interactions enable the observed switching.
Site‐Selective Cysteine–Cyclooctyne Conjugation
Authors: Zhang Chi , Dai Peng , Vinogradov Alexander A. , Gates Zachary P. , Pentelute Bradley L.
Published: March 2018

We report a site‐selective cysteine–cyclooctyne conjugation reaction between a seven‐residue peptide tag (DBCO‐tag, Leu‐Cys‐Tyr‐Pro‐Trp‐Val‐Tyr) at the N or C terminus of a peptide or protein and various aza‐dibenzocyclooctyne (DBCO) reagents. Compared to a cysteine peptide control, the DBCO‐tag increases the rate of the thiol–yne reaction 220‐fold, thereby enabling selective conjugation of DBCO‐tag to DBCO‐linked fluorescent probes, affinity tags, and cytotoxic drug molecules. Fusion of DBCO‐tag with the protein of interest enables regioselective cysteine modification on proteins that contain multiple endogenous cysteines; these examples include green fluorescent protein and the antibody trastuzumab. This study demonstrates that short peptide tags can aid in accelerating bond‐forming reactions that are often slow to non‐existent in water.
Inhibition of α‐Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends
Authors: Shvadchak Volodymyr V. , Afitska Kseniia , Yushchenko Dmytro A.
Published: March 2018

Misfolding of the protein α‐synuclein (αSyn) into amyloid fibrils plays a central role in the development of Parkinson's disease. Most approaches for the inhibition of αSyn fibril formation are based on stabilizing the native monomeric form of the protein or destabilizing the fibrillized misfolded form. They require high concentrations of inhibitor and therefore cannot be easily used for therapies. In this work, we designed an inhibitor (Inh‐β) that selectively binds the growing ends of αSyn fibrils and creates steric hindrance for the binding of monomeric αSyn. This approach permits the inhibition of fibril formation at Inh‐β concentrations (IC50=850 nm) much lower than the concentration of monomeric αSyn. We studied its kinetic mechanism in vitro and identified the reactions that limit inhibition efficiency. It is shown that blocking of αSyn fibril ends is an effective approach to inhibiting fibril growth and provides insights for the development of effective inhibitors of αSyn aggregation.
Photoinduced Copper‐Catalyzed Coupling of Terminal Alkynes and Alkyl Iodides
Authors: Hazra Avijit , Lee Mitchell T. , Chiu Justin F. , Lalic Gojko
Published: March 2018

We have developed a photoinduced copper‐catalyzed alkylation of terminal alkynes with primary, secondary, or tertiary alkyl iodides as electrophiles. The reaction has a broad substrate scope and can be successfully performed in the presence of ester, nitrile, aryl halide, ketone, sulfonamide, epoxide, alcohol, and amide functional groups. The alkylation is promoted by blue light (λ≈450 nm) and proceeds at room temperature in the absence of any additional metal catalysts. The use of a terpyridine ligand is essential for the success of the reaction and is shown to prevent photoinduced copper‐catalyzed polymerization of the starting materials.
Iridium‐Catalyzed Sequential Silylation and Borylation of Heteroarenes Based on Regioselective C−H Bond Activation
Authors: Murai Masahito , Nishinaka Naoki , Takai Kazuhiko
Published: March 2018

An iridium‐catalyzed regioselective sequential silylation and borylation of heteroarenes was developed, which represents a rare example of unsymmetrical intermolecular C−H bond difunctionalization through the introduction of two different functionalities during a one‐pot transformation. Although the substrate scope for the dehydrogenative silylation of heteroarenes has been limited mainly to electron‐rich five‐membered rings, the current reaction proceeds with both electron‐rich and electron‐deficient heteroarenes with the aid of heteroatom‐directing C−H bond activation. The regioselectivity of the second borylation was controlled by both steric factors and the electronic effect of the silyl group installed in the first step. In combination with the classic cross‐coupling reaction, this method provides rapid access to multisubstituted heteroarenes.
Measuring Spin Relaxation Rates Using Satellite Exchange NMR Spectroscopy
Authors: Robertson Gerard P. , Odell Barbara , Kuprov Ilya , Dixon Darren J. , Claridge Tim D. W.
Published: March 2018

An approach to the indirect measurement of nuclear spin relaxation rates of low‐magnetogyric ratio (γ) nuclei using the process of satellite exchange is described. The method does not require the observation of, or even the ability to provide radio‐frequency pulses to, the low‐γ nucleus, but requires this to be scalar coupled to an NMR observable nucleus, such as 31P or 1H, making it especially attractive for the study of diamagnetic transition metals. In situations where spin relaxation is dominated by chemical shift anisotropy (CSA), the determination of the longitudinal spin relaxation time constant (T1) of the metal becomes possible, as illustrated for 195Pt and 107/109Ag.
Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers
Authors: Feng Guang‐Shou , Chen Mu‐Wang , Shi Lei , Zhou Yong‐Gui
Published: March 2018

A facile access to optically active cyclic ureas was developed through palladium‐catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin‐2(1H)‐one, acid‐catalyzed isomerization of enamine–imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity.
Fluorogenic Ag+–Tetrazolate Aggregation Enables Efficient Fluorescent Biological Silver Staining
Authors: Xie Sheng , Wong Alex Y. H. , Kwok Ryan T. K. , Li Ying , Su Huifang , Lam Jacky W. Y. , Chen Sijie , Tang Ben Zhong
Published: March 2018

Silver staining, which exploits the special bioaffinity and the chromogenic reduction of silver ions, is an indispensable visualization method in biology. It is a most popular method for in‐gel protein detection. However, it is limited by run‐to‐run variability, background staining, inability for protein quantification, and limited compatibility with mass spectroscopic (MS) analysis; limitations that are largely attributed to the tricky chromogenic visualization. Herein, we reported a novel water‐soluble fluorogenic Ag+ probe, the sensing mechanism of which is based on an aggregation‐induced emission (AIE) process driven by tetrazolate‐Ag+ interactions. The fluorogenic sensing can substitute the chromogenic reaction, leading to a new fluorescence silver staining method. This new staining method offers sensitive detection of total proteins in polyacrylamide gels with a broad linear dynamic range and robust operations that rival the silver nitrate stain and the best fluorescent stains.
Platzierung einzelner Proteine in den SERS‐Hot‐Spots selbstorganisierter Silbernanolinsen
Authors: Heck Christian , Kanehira Yuya , Kneipp Janina , Bald Ilko
Published: March 2018

Diese Studie demonstriert die Bottom‐up‐Synthese von Silbernanolinsen. Ein robustes Beschichtungsprotokoll ermöglichte die Funktionalisierung unterschiedlich großer Silbernanopartikel mit einzelsträngiger DNA unterschiedlicher Sequenz. Derartig beschichtete Partikel mit Durchmessern von 10 nm, 20 nm und 60 nm wurden mithilfe von DNA‐Origami‐Gerüsten zu Silbernanolinsen angeordnet. Ein einzelnes Molekül des Proteins Streptavidin ist in demjenigen Spalt zwischen den Partikeln immobilisiert worden, der die höchste Feldverstärkung zur Verfügung stellt. Streptavidin war dabei mit Alkin‐Gruppen modifiziert und fungierte als Modellanalyt in Experimenten zur oberflächenverstärkten Raman‐Streuung (SERS). Korrelierte Raman‐ und Rasterkraftmikroskopie‐Messungen ermöglichten die Aufnahme von SERS‐Signalen der Alkingruppen eines einzelnen Streptavidins, von einer einzelnen Silbernanolinse. Diese diskreten, selbstähnlichen Silbernanopartikelaggregate versprechen vielfältige Anwendungen im Feld der Plasmonik.
Alkyl Ethers as Traceless Hydride Donors in Brønsted Acid Catalyzed Intramolecular Hydrogen Atom Transfer
Authors: Gandamana Dhika Aditya , Wang Bin , Tejo Ciputra , Bolte Benoit , Gagosz Fabien , Chiba Shunsuke
Published: March 2018

A new protocol for the deoxygenation of alcohols and the hydrogenation of alkenes under Brønsted acid catalysis has been developed. The method is based on the use of either a benzyl or isopropyl ether as a traceless hydrogen‐atom donor, and involves an intramolecular hydride transfer as a key step, which is achieved in a regio‐ and stereoselective manner.
Indyllithium and the Indyl Anion [InL]−: Heavy Analogues of N‐Heterocyclic Carbenes
Authors: Schwamm Ryan J. , Anker Mathew D. , Lein Matthias , Coles Martyn P. , Fitchett Christopher M.
Published: March 2018

Reduction of the indate complex In(NONAr)(μ‐Cl)2Li(OEt2)2 (NONAr=[O(SiMe2NAr)2]2−; Ar=2,6‐iPr2C6H3) with sodium generates the InII diindane species [In(NONAr)]2. Further reduction with a mixture of potassium and [2.2.2]crypt affords the InI N‐heterocyclic indyl anion [In(NONAr)]−, which crystallizes with a non‐contacted [K([2.2.2]crypt)]+ cation. The indyl anion can also be isolated as the indyllithium compound In(NONAr)(Li{THF}3), which contains an In−Li bond. Density functional theory calculations show that the HOMO of the indyl anion is a metal‐centred lone pair, and preliminary reactivity studies confirm its nucleophilic behaviour.
Localizing Antifungal Drugs to the Correct Organelle Can Markedly Enhance their Efficacy
Authors: Benhamou Raphael I. , Bibi Maayan , Berman Judith , Fridman Micha
Published: March 2018

A critical aspect of drug design is optimal target inhibition by specifically delivering the drug molecule not only to the target tissue or cell but also to its therapeutically active site within the cell. This study demonstrates, as a proof of principle, that drug efficacy can be increased considerably by a structural modification that targets it to the relevant organelle. Specifically, by varying the fluorescent dye segment an antifungal azole was directed from the fungal cell mitochondria to the endoplasmic reticulum (ER), the organelle that harbors the drug target. The ER‐localized azole displayed up to two orders of magnitude improved antifungal activity and also dramatically reduced the growth of drug‐tolerant fungal subpopulations in a panel of Candida species, which are the most prevalent causes of serious human fungal infections. The principle underlying the “target organelle localization” approach provides a new paradigm to improve drug potency and replenish the limited pipeline of antifungal drugs.
Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Total Synthesis of (−)‐17‐nor‐Excelsinidine
Authors: Jarret Maxime , Tap Aurélien , Kouklovsky Cyrille , Poupon Erwan , Evanno Laurent , Vincent Guillaume
Published: March 2018

We report the first total synthesis of (−)‐17‐nor‐excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4−C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium–acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution on a 16‐chlorolactam with the N4 nitrogen atom or a direct I2‐mediated N4−C16 oxidative coupling from the enolate of geissoschizine.
Transition‐Metal‐Like Behavior of Monovalent Boron Compounds: Reduction, Migration, and Complete Cleavage of CO at a Boron Center
Authors: Wang Hao , Wu Linlin , Lin Zhenyang , Xie Zuowei
Published: March 2018

The borylene–carbonyl moiety in [bis(silylene)B(CO)][WBr(CO)5] shows diverse reactivity. Reduction, migration, and complete cleavage of CO have been observed at the boron center, leading to the formation of new types of borylenes. These reactions not only serve as new methods for the synthesis of various stable borylenes, but also demonstrate that main‐group‐element compounds can mimic the behavior of transition‐metal complexes.
Sulfoximidations of Benzylic C−H bonds by Photocatalysis
Authors: Wang Han , Zhang Duo , Bolm Carsten
Published: March 2018

An efficient photocatalytic functionalization of compounds with benzylic C−H bonds by sulfoximidation in visible light is described. The mild reaction conditions allow the use of a broad array of substrates, including diarylmethane, alkyl arenes, arylacetonitrile, 2‐arylacetate, and alkynyl aryl methanes. The sulfoximidation process is highly chemoselective and leads to the corresponding sulfoximines in generally good yields. Mechanistic investigations suggested the intermediacy of sulfoximidoyl radicals.
Placement of Single Proteins within the SERS Hot Spots of Self‐Assembled Silver Nanolenses
Authors: Heck Christian , Kanehira Yuya , Kneipp Janina , Bald Ilko
Published: March 2018

This study demonstrates the bottom‐up synthesis of silver nanolenses. A robust coating protocol enabled the functionalization of differently sized silver nanoparticles with DNA single strands of orthogonal sequence. Coated particles 10 nm, 20 nm, and 60 nm in diameter were self‐assembled by DNA origami scaffolds to form silver nanolenses. Single molecules of the protein streptavidin were selectively placed in the gap of highest electric field enhancement. Streptavidin labelled with alkyne groups served as model analyte in surface‐enhanced Raman scattering (SERS) experiments. By correlated Raman mapping and atomic force microscopy, SERS signals of the alkyne labels of a single streptavidin molecule, from a single silver nanolens, were detected. The discrete, self‐similar aggregates of solid silver nanoparticles are promising for plasmonic applications.
Hydrido Complexes of Calcium: A New Family of Molecular Alkaline‐Earth‐Metal Compounds
Authors: Mukherjee Debabrata , Schuhknecht Danny , Okuda Jun
Published: March 2018

The application of solid calcium hydride CaH2 has been mostly confined to its use as a desiccant, although its catalytic activity has long been known. Since the first isolation of a well‐defined molecular calcium hydride in 2006, the past decade has witnessed a gradual emergence of this new family of compounds. Although the detrimental Schlenk equilibrium has kept the number of examples low, the novelty of their reactivity, especially in small‐molecule activation, holds great promise. This Minireview gives an overview of the molecular calcium hydrides reported to date, highlighting their synthesis, structure, and reactivity.
Custom‐Made Ceria Nanoparticles Show a Neuroprotective Effect by Modulating Phenotypic Polarization of the Microglia
Authors: Zeng Feng , Wu Yingwei , Li Xinwei , Ge Xiaojiao , Guo Qinghua , Lou Xiaobing , Cao Zhonglian , Hu Bingwen , Long Nicholas J. , Mao Ying , Li Cong
Published: March 2018

The neuroprotective effect of ceria nanoparticles in the context of brain disorders has been explained by their antioxidant effect. However, the in‐depth mechanism remains unknown. As resident immune cells in the brain, microglia exert a variety of functional reprogramming termed as polarization in response to stress stimuli. Herein, custom‐made ceria nanoparticles were developed and found to scavenge multiple reactive oxygen species with extremely high efficiency. These nanoparticles drove microglial polarization from a pro‐inflammatory phenotype to an anti‐inflammatory phenotype under pathological conditions. Pretreatment of these nanoparticles changed the microglial function from detrimental to protective for the neuronal cells by blocking the pro‐inflammatory signaling. This work not only helps to elucidate the mechanism of ceria‐nanoparticle‐mediated neuroprotection but also provides a new strategy to rebalance the immuno‐environment by switching the equilibrium of the phenotypic activation of microglia.