bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Outcomes of Arthroscopic Treatment of Freiberg Disease
Authors: Kim Jong-Kil , Kim Do-Yeon , Oh Jong-Sung , Ko Dong-ill , Lee Kwang-Bok
Published: July 2024

Background: Surgical treatment for Freiberg disease (also known as avascular necrosis of the metatarsal head) has not been completely defined. This retrospective study evaluated short-term outcomes after arthroscopic treatment of Freiberg disease.

Methods: From 2015 to 2019, 13 patients (15 feet) diagnosed as having Freiberg disease were enrolled for arthroscopic surgery. Feet were divided based on the Smillie classification system (two with stage I, eight with stage II, three with stage III, one with stage IV, and one with stage V). Arthroscopic interventions, including synovectomy, debridement, chondroplasty, microfracture, and loose body removal, were performed without considering the Smillie classification stage. Radiologic outcomes were evaluated by radiography (preoperatively and 3, 6, and 12 months postoperatively) and magnetic resonance imaging (preoperatively and 12 months postoperatively). Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal (MTP)–interphalangeal score and the visual analog scale (VAS) score. The MTP joint range of motion was measured using a goniometer preoperatively and postoperatively.

Results: Radiologic studies showed no evidence of osteonecrosis progression in postoperative 12-month radiographs of any patients. Postoperative 12-month magnetic resonance images showed reduction of bone marrow edema, irregularity of subchondral bone, and cartilage defects in all patients. Significant improvements in AOFAS and VAS scores occurred at all postoperative time points compared with preoperative scores (P = .001). The MTP joint range of motion also showed improvement at last follow-up (P = .001).

Conclusions: Arthroscopic surgery for Freiberg disease showed excellent clinical outcomes, MTP joint range of motion, and short-term outcomes regardless of stage (Smillie classification) in radiologic evaluation.
Senior Podiatrists in Solo Practice are High Performers of Nail Excisions
Authors: Rivin Gabrielle M. , Vlahovic Tracey C. , Hill Rachel C. , Fleischer Alan B. , Lipner Shari R.
Published: July 2024

Background: Nail excisions are indicated for onychocryptosis and nail spicules. They are technically demanding and require a refined skill set. We aimed to characterize practice patterns of US providers performing nail excisions.

Methods: We conducted a retrospective analysis of Medicare provider use and payment data, part D, for all claims of partial or complete nail/nail matrix excision with/without nail plate removal/destruction (current procedural terminology code 11750). High performers were defined as providers performing annual nail excisions 2 standard deviations above the mean. We analyzed demographic risk factors for nail excision high performers, including practice location, years of experience, household median income, practice type, and provider gender. Statistical analysis was conducted in SAS v9.4, with values of P < .05 considered statistically significant.

Results: Providers (n = 32,279) and high performers (n = 942) performed mean 34.7 and 173 nail excisions annually. Unsurprisingly, podiatrists constituted 99.7% of all nail excision performers. Providers in the South versus Midwest and Northeast were more often nail excision high performers (odds ratio [OR], 1.95; P < .0001, and OR, 1.46; P < .0001). Solo versus group practitioners were more likely, respectively, to be nail excision high performers (OR, 2.15; P < .0001). With linear regression analysis, for every 10-year increase in years of provider experience, there was an increase of 1.2 nail excisions annually per provider (P < .0001). For every $100,000 increase in household median income of practice location, there was a decrease of 9.9 nail excisions annually per provider.

Conclusions: Southern podiatrists, podiatrists with more years of experience, solo practitioners, and those practicing in regions with lower household median incomes were more likely to perform higher numbers of nail excisions. Identifying performance trends among podiatrists can help podiatrists understand how their performance of nail excisions compares to other podiatrists across the country.
Validation and Utility of a Novel Foot Offloading Device: Improving Pain and Function
Authors: Asaad Malke , Gusenoff Beth , Gusenoff Jeffrey A.
Published: July 2024

Background: Foot pain is a common presentation, and management is generally geared toward pressure offloading. Although several pressure offloading devices exist on the market, the search for the optimal device is ongoing.

Methods: We recently developed PopSole, an inexpensive, simple, balanced offloading insole focused on reducing targeted foot pain. We conducted a prospective validation study of patients with foot pain lasting longer than 6 months to assess the durability and efficacy of the device with follow-up scheduled at 2 weeks, 4 weeks, 2 months, and 3 months. Patient-reported outcomes were collected using multiple validated surveys. Fifteen patients were enrolled in this study.

Results: At 4 weeks, pain, function, and quality of life across all surveys showed statistically significant improvement. For the 6 patients with long-term outcomes (3 months), patients reported improvement in their pain, function, and quality of life across all surveys, which were significant in the Mayo survey (P = .018), the Manchester Foot Pain and Disability Index (P = .014), the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale (P = .032), the Foot and Ankle Ability Measure activities of daily living (P = .009), and the Pittsburgh foot survey (P = .01); the Foot and Ankle Ability Measure sports approached statistical significance (P = .058).

Conclusions: The PopSole is a durable and effective device to relieve foot pain, improve function, and improve quality of life for up to 3 months of use.
Cholinergic input to mouse visual cortex signals a movement state and acutely enhances layer 5 responsiveness
Authors: Yogesh Baba , Keller Georg B
Published: July 2024

Acetylcholine is released in visual cortex by axonal projections from the basal forebrain. The signals conveyed by these projections and their computational significance are still unclear. Using two-photon calcium imaging in behaving mice, we show that basal forebrain cholinergic axons in the mouse visual cortex provide a binary locomotion state signal. In these axons, we found no evidence of responses to visual stimuli or visuomotor prediction errors. While optogenetic activation of cholinergic axons in visual cortex in isolation did not drive local neuronal activity, when paired with visuomotor stimuli, it resulted in layer-specific increases of neuronal activity. Responses in layer 5 neurons to both top-down and bottom-up inputs were increased in amplitude and decreased in latency, whereas those in layer 2/3 neurons remained unchanged. Using opto- and chemogenetic manipulations of cholinergic activity, we found acetylcholine to underlie the locomotion-associated decorrelation of activity between neurons in both layer 2/3 and layer 5. Our results suggest that acetylcholine augments the responsiveness of layer 5 neurons to inputs from outside of the local network, possibly enabling faster switching between internal representations during locomotion.
Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics
Authors: Xie Peng , Jiang Xu , He Jingjing , Pan Qingyun , Yang Xianfa , Zheng Yanying , Fan Wenli , Wu Chen , Zheng Weiheng , Fang Ke , Si Shuhan , Zhu Shiqi , Yang Yi , Zhong Tao P , Yang Zhongzhou , Wei Ke , Xie Wei , Jing Naihe , Luo Zhuojuan , Lin Chengqi
Published: July 2024

The mammalian heart is formed from multiple mesoderm-derived cell lineages. However, it remains largely unknown when and how the specification of mesoderm towards cardiac lineages is determined. Here, we systematically depict the transcriptional trajectories toward cardiomyocyte in early mouse embryo, and characterize the epigenetic landscapes underlying the early mesodermal lineage specification by single-cell multi-omics analyses. The analyses also reveal distinct core regulatory networks (CRN) in controlling specification of mesodermal lineages. We further demonstrate the essential role HAND1 and FOXF1 in driving the earliest cardiac progenitors specification. These key transcription factors occupy at distinct enhancers, but function synergistically and hierarchically to regulate the expression of cardiac-specific genes. In addition, HAND1 is required for exiting from the nascent mesoderm program, while FOXF1 is essential for driving cardiac differentiation during MJH specification. Our findings establish transcriptional and epigenetic determinants specifying the early cardiac lineage, providing insights for the investigation of congenital heart defects.
Identification of Suitable Target/E3 Ligase Pairs for PROTAC Development using a Rapamycin-induced Proximity Assay (RiPA)
Authors: Adhikari Bikash , Schneider Katharina , Diebold Mathias , Sotriffer Christoph , Wolf Elmar
Published: July 2024

The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest. As more and more ligands for novel E3 ligases are discovered, the chemical effort to identify the best E3 ligase for a given target is exploding. Therefore, a genetic system to identify degradation-causing E3 ligases and suitable target/E3 ligase pairs is urgently needed. Here we used the well-established dimerization of the FKBP12 protein and FRB domain by rapamycin to bring the target protein WDR5 into proximity with candidate E3 ligases. Strikingly, this rapamycin-induced proximity assay (RiPA) revealed that VHL, but not Cereblon, is able to induce WDR5 degradation - a finding previously made by PROTACs, demonstrating its predictive power. By optimizing the steric arrangement of all components and fusing the target protein with a minimal luciferase, RiPA can identify the ideal E3 for any target protein of interest in living cells, significantly reducing and focusing the chemical effort in the early stages of PROTAC development.
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Authors: Rademacher Katerina , Doric Zak , Haddad Dominik , Mamaligas Aphroditi , Liao Szu-Chi , Creed Rose B. , Kano Kohei , Chatterton Zac , Fu Yuhong , Garcia Joseph H. , Vance Victoria , Sei Yoshitaka , Kreitzer Anatol , Halliday Glenda M , Nelson Alexandra B. , Margolis Elyssa B. , Nakamura Ken
Published: July 2024

Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered in PD, but we understand little about if or how chronic changes in activity may contribute to degeneration. To address this question, we developed a chemogenetic (DREADD) mouse model to chronically increase DA neuron activity, and confirmed this increase using
ex vivo
electrophysiology. Chronic hyperactivation of DA neurons resulted in prolonged increases in locomotor activity during the light cycle and decreases during the dark cycle, consistent with chronic changes in DA release and circadian disturbances. We also observed early, preferential degeneration of SNc projections, recapitulating the PD hallmarks of selective vulnerability of SNc axons and the comparative resilience of ventral tegmental area axons. This was followed by eventual loss of midbrain DA neurons. Continuous DREADD activation resulted in a sustained increase in baseline calcium levels, supporting an important role for increased calcium in the neurodegeneration process. Finally, spatial transcriptomics from DREADD mice examining midbrain DA neurons and striatal targets, and cross-validation with human patient samples, provided insights into potential mechanisms of hyperactivity-induced toxicity and PD. Our results thus reveal the preferential vulnerability of SNc DA neurons to increased neural activity, and support a potential role for increased neural activity in driving degeneration in PD.
Characterization of binding kinetics and intracellular signaling of new psychoactive substances targeting cannabinoid receptor using transition-based reweighting method
Authors: Dutta Soumajit , Shukla Diwakar
Published: July 2024

New psychoactive substances (NPS) targeting cannabinoid receptor 1 pose a significant threat to society as recreational abusive drugs that have pronounced physiological side effects. These greater adverse effects compared to classical cannabinoids have been linked to the higher downstream
β
-arrestin signaling. Thus, understanding the mechanism of differential signaling will reveal important structure-activity relationship essential for identifying and potentially regulating NPS molecules. In this study, we simulate the slow (un)binding process of NPS MDMB-Fubinaca and classical cannabinoid HU-210 from CB
1
using multi-ensemble simulation to decipher the effects of ligand binding dynamics on downstream signaling. The transition-based reweighing method is used for the estimation of transition rates and underlying thermodynamics of (un)binding processes of ligands with nanomolar affinities. Our analyses reveal major interaction differences with transmembrane TM7 between NPS and classical cannabinoids. A variational autoencoder-based approach, neural relational inference (NRI), is applied to assess the allosteric effects on intracellular regions attributable to variations in binding pocket interactions. NRI analysis indicate a heightened level of allosteric control of NPxxY motif for NPS-bound receptors, which contributes to the higher probability of formation of a crucial triad interaction (Y
7.53
-Y
5.58
-T
3.46
) necessary for stronger
β
-arrestin signaling. Hence, in this work, MD simulation, data-driven statistical methods, and deep learning point out the structural basis for the heightened physiological side effects associated with NPS, contributing to efforts aimed at mitigating their public health impact.
Tonotopy is not preserved in a descending stage of auditory cortex
Authors: Gu Miaoqing , Liang Shanshan , Zhu Jiahui , Li Ruijie , Liu Ke , Wang Xuanyue , Ohl Frank , Zhang Yun , Liao Xiang , Zhang Chunqing , Jia Hongbo , Zhou Yi , Zhang Jianxiong , Chen Xiaowei
Published: July 2024

Previous studies based on layer specificity suggest that ascending signals from the thalamus to sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mapped tone response properties of two groups of cortical neurons in the primary auditory cortex (A1), based on the relationship between their specific connections to other regions and their function in ascending (thalamocortical recipient, TR neurons) or descending (corticothalamic, CT neurons) auditory information. A clear tonotopic gradient was observed among TR, but not CT neurons. Additionally, CT neurons exhibited markedly higher heterogeneity in their frequency tuning and had broader bandwidth than TR neurons. These results reveal that the information flow descending from A1 to thalamus via CT neurons does not arrange tonotopically, suggesting that the descending information flow possibly contributes to higher-order feedback processing of diverse auditory inputs.
Comparison of Cognitive Performance, Stress, Body Mass Index, and Lung Functions in Exercising and Non Exercising Medical Students: A Cross-sectional Study
Authors: Ankireddy Ritish Reddy , Bharath T , Vageesh Vijaya
Published: July 2024

Introduction: Stress is an inherent part of the human experience, especially among medical students, due to academic pursuits and social commitments. The present study explores the intricate relationship of cognition with perceived stress levels, lung function, and Body Mass Index (BMI) in exercising and non exercising medical students. Aim: To find out and compare the levels of stress, cognition, BMI, and lung function in exercising and non exercising medical students. Materials and Methods: This cross-sectional study was conducted at the Department of Physiology, JSS Medical College, Constituent College of JSSAHER, Mysuru, Karnataka, India over a span of two months from February 2021 to April 2021. It included 110 participants categorised into an exercising group and a non exercising group. Stress and cognition were measured using the Perceived Stress Scale 10 (PSS-10) and the Modified Mini-mental State Examination (3MS), respectively. The BMI was calculated using Quetelet’s index. Pulmonary function was measured using a computerised spirometer. Associations were determined using a Student’s t-test, with p<0.05 considered significant. Results: The mean PSS-10 score for exercising students (11.36±3.67) was significantly lower compared to non exercising students (20.71±4.61). The 3MS score of exercisers (97.33±1.73) was significantly higher compared to nonexercisers (94.02±1.40). The mean values of pulmonary functions namely Forced Expiratory Volume 1 (FEV1) (3.43±0.71 L), Forced Vital Capacity (FVC) (3.88±0.76 L), and FEV1/FVC (87.94±2.73%) in exercisers, were significantly better than the values for non-exercisers: FEV1 (3.00±0.67 L), FVC (3.48±0.71 L), and FEV1/FVC (85.86±2.75%). The mean BMI of exercisers (21.45±1.43 kg/m2 ) was significantly lower than that of nonexercisers (23.03±1.35 kg/m2 ). Conclusion: Participants who exercise regularly have better cognition, lower stress levels, a healthier BMI, and better lung function than their non exercising counterparts.
IoT-based Facial Recognition Door Lock with Push Button Combination
Authors: Syarifuddin  , Syam Husain , Syafar Faisal
Published: July 2024

A common issue in many households is the management of door keys, which can often be lost, damaged, or forgotten. This problem can be particularly frustrating when family members arrive home to find they cannot enter their residence. One potential solution to this problem is the implementation of a facial recognition system, which can be used by multiple family members to gain access to their home. The proposed system utilizes an intelligent minicomputer with a dual function, serving as both a Central Processing Unit (CPU) and a monitor screen display connected via an HDMI to VGA adapter. Additionally, the system incorporates a RealVNC Viewer (Virtual Network Computer) as a remote desktop application, accessible via a laptop or Android device. The primary aim of this research is to develop a facial recognition system that can unlock a house door by detecting and matching the user's face with stored data. The minicomputer, acting as a microcontroller, captures the user's face through a camera and compares it with the photo database. If a match is found, the system grants access and displays information on the Android device, indicating whether the user is known or unknown. This study employs a Research and Development (R&D) approach to enhance the effectiveness and security of home control systems using an internet network and Android devices. The system successfully detects facial objects within the camera's range, with the detection point area turning left, right, or focusing towards the front of the rectangular frame. The buzzer indicator sounds when the door lock is open. The system has been tested with multiple users, with local detection distance and over a well-validated network.
Analysis of Marketing Channels of Papaya in Middle Gujarat, India
Authors: Shekhaliya Viraj , Mishra Snehal
Published: July 2024

This study investigates the marketing channels, price spread, and constraints faced by papaya producer and intermediaries in the middle Gujarat region, specifically in the districts of Vadodara, Anand, and Ahmedabad. A total of 150 farmers, 25 papaya wholesalers, and 25 papaya retailers were surveyed randomly using structured questionnaires to collect data on marketing channels, price spread, and constraints faced. Three main marketing channels were identified: Channel I (Farmer – Pre-harvest contractor – Wholesaler cum commission Agent – Retailer – Consumer), Channel II (Farmer – Wholesaler cum commission Agent – Retailer – Consumer), and Channel III (Farmer – Retailer – Consumer). The study reveals that Channel III is the most efficient and beneficial for papaya farmers, offering the highest net price, the lowest price spread, and the best marketing efficiency. Price spreads were notably high in Channel I at Rs. 5000 per quintal, compared to Rs. 4670 per quintal in Channel II and a significantly reduced Rs. 2835 per quintal in Channel III. Constraints faced by papaya producers include disease and pests especially viral attacks, uncertain weather conditions, and high initial investment. Wholesalers and retailers face challenges related to transportation, wastage/spoilage, and lack of storage facilities. The findings suggest that adopting Channel III can enhance profitability for papaya farmers and improve the efficiency of the marketing chain. The study identifies the need for optimizing marketing channels and addressing constraints to ensure fair profit distribution and marketing of papaya.
Preliminary evaluation of S‐NPP VIIRS aerosol optical thickness
Authors: Liu Hongqing , Remer Lorraine A. , Huang Jingfeng , Huang Ho‐Chun , Kondragunta Shobha , Laszlo Istvan , Oo Min , Jackson John M
Published: March 2014

The Visible Infrared Imaging Radiometer Suite (VIIRS) is the next‐generation polar‐orbiting operational environmental sensor with a capability for global aerosol observations. The VIIRS aerosol Environmental Data Record (EDR) is expected to continue the decade‐long successful multispectral aerosol retrieval from the NASA's Earth Observing System Moderate Resolution Imaging Spectroradiometer (MODIS) for scientific research and applications. Since the launch of the Suomi National Polar‐orbiting Partnership (S‐NPP), the VIIRS aerosol calibration/validation team has been continuously monitoring, evaluating, and improving the performance of VIIRS aerosol retrievals. In this study, the VIIRS aerosol optical thickness (AOT) at 550 nm EDR at current Provisional maturity level is evaluated by comparing it with MODIS retrievals and measurements from the Aerosol Robotic Network (AERONET) and the Maritime Aerosol Network (MAN). The VIIRS global mean AOT at 550 nm differs from that of MODIS by approximately −0.01 over ocean and 0.03 over land (0.00 and −0.01 for the collocated retrievals) but shows larger regional biases. Global validation with AERONET and with MAN measurements shows biases of 0.01 over ocean and −0.01 over land, with about 64% and 71% of retrievals falling within the expected uncertainty range established by MODIS over ocean (±(0.03 + 0.05AOT)) and over land (±(0.05 + 0.15AOT)), respectively. The VIIRS retrievals over land exhibit slight overestimation over vegetated surfaces and underestimation over soil‐dominated surfaces. These results show that the VIIRS AOT at 550 nm product provides a solid global data set for quantitative scientific investigations and environmental monitoring.
Climate models show increasing Arctic cyclone activity
Authors: Schultz Colin
Published: March 2014

Winter in the Arctic is not only cold and dark—it is also storm season, when hurricane‐like Arctic cyclones traverse northern waters. Arctic cyclones predominantly occur in subpolar regions, around Iceland or the Aleutian Islands. Like all cyclones, Arctic cyclones are characterized by strong localized drops in sea level pressure. One expected consequence of global climate change is an Arctic‐wide decrease in sea level pressure, which would serve to increase extreme Arctic cyclone activity, including powerful storms that can sometimes hit in the spring and fall.
Synthesis of Pyrazolo[1,2‐a]cinnolines via a Rhodium‐Catalyzed Oxidative Coupling Approach
Authors: Xing Li , Fan Zhoulong , Hou Chengyu , Yong Guoping , Zhang Ao
Published: March 2014

An efficient synthetic strategy for the unique class of pyrazolo[1,2‐a]cinnolines was developed through a rhodium‐catalyzed oxidative coupling of N‐aryl‐1H‐pyrazol‐5(4H)‐ones with internal alkynes. This protocol features use of the pyrazolone function in the substrate as an intrinsic directing group, hexafluoroisopropyl alcohol (HFIP) as the solvent, and mild reaction conditions as well as a wide substrate scope.

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Application of taylor dispersion technique to measure mutual diffusion coefficient in hexane + bitumen system
Authors: Ghanavati Mohsen , Hassanzadeh Hassan , Abedi Jalal
Published: March 2014

A novel approach with fewer technical and analytic limitations in liquid solvent‐bitumen diffusion studies is used in this article. The Taylor dispersion technique was selected for its convenient short run time experiments and reliable data analysis to find mutual diffusion coefficients in a hexane + bitumen mixture. For the first time, the infinite‐dilution molecular diffusion coefficients of bitumen in hexane were measured in both the presence and relative absence of asphaltene particles in the solution at atmospheric pressure and temperatures of 303.15, 310.15, and 317.15 K. The polydisperse nature of bitumen was clearly revealed. Results were compared with common predictive tools. Also, the asphaltene surface charge in the hexane precipitating solvent was demonstrated. Through concentration dependency investigations at atmospheric pressure and 303.15 K, it was determined that the mutual diffusion coefficients monotonically decrease as the viscosity of mixture increases within the studied 0–34% volumetric concentration of bitumen. The Taylor dispersion technique shows great potential for diffusion studies of liquid solvent‐bitumen systems. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2670–2682, 2014
Brain injury in premature neonates: A primary cerebral dysmaturation disorder?
Authors: Back Stephen A. , Miller Steven P.
Published: March 2014

With advances in neonatal care, preterm neonates are surviving with an evolving constellation of motor and cognitive disabilities that appear to be related to widespread cellular maturational disturbances that target cerebral gray and white matter. Whereas preterm infants were previously at high risk for destructive brain lesions that resulted in cystic white matter injury and secondary cortical and subcortical gray matter degeneration, contemporary cohorts of preterm survivors commonly display less severe injury that does not appear to involve pronounced glial or neuronal loss. Nevertheless, these milder forms of injury are also associated with reduced cerebral growth. Recent human and experimental studies support that impaired cerebral growth is related to disparate responses in gray and white matter. Myelination disturbances in cerebral white matter are related to aberrant regeneration and repair responses to acute death of premyelinating late oligodendrocyte progenitors (preOLs). In response to preOL death, early oligodendrocyte progenitors rapidly proliferate and differentiate, but the regenerated preOLs fail to normally mature to myelinating cells required for white matter growth. Although immature neurons appear to be more resistant to cell death from hypoxia–ischemia than glia, they display widespread disturbances in maturation of their dendritic arbors, which further contribute to impaired cerebral growth. These complex and disparate responses of neurons and preOLs thus result in large numbers of cells that fail to fully mature during a critical window in development of neural circuitry. These recently recognized forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic directions centered on reversal of the processes that promote dysmaturation. Ann Neurol 2014;75:469–486
Molekulare CuII‐O‐CuII‐Komplexe: Stille Wasser sind tief
Authors: Haack Peter , Limberg Christian
Published: March 2014

Die Forschung zur O2‐Aktivierung an ligierten CuI‐Ionen wird durch ihre biologische Relevanz und die Suche nach effizienten Oxidationskatalysatoren getrieben. Ein in diesem Zusammenhang selten beobachteter Reaktionspfad ist die ungewöhnliche Bildung von CuII‐O‐CuII‐Einheiten: Ein einzelner, zwischen zwei CuII‐Ionen gebundener Oxoligand erfährt eine beträchtliche Elektronendichte, die Cu2O‐Komplexe sehr reaktiv und somit nur schwer zugänglich macht. Daher – und auch wegen der scheinbar fehlenden biologischen Bedeutung – wurden bisher nur wenige solche Verbindungen synthetisiert und charakterisiert. Kürzlich jedoch wurden CuII‐O‐CuII‐Einheiten als aktive Spezies für die selektive Oxidation von Methan zu Methanol sowohl auf der Oberfläche eines kupferhaltigen Zeoliths als auch im aktiven Zentrum der Methanmomooxygenase diskutiert. Dieser Kurzaufsatz soll einen Überblick über den aktuellen Wissensstand bezüglich niedermolekularer Systeme bieten, mit einem Fokus auf ihren spektroskopischen Eigenschaften und Reaktivitäten.
Synthesis and characterization of high‐molecular weight aliphatic polyesters from monomers derived from renewable resources
Authors: Kong Xiaohua , Qi Hong , Curtis Jonathan M.
Published: March 2014

A series of high‐molecular weight aliphatic polyesters have been synthesized, at temperatures of < 200°C, through a polycondensation reaction between 1,4‐butanediol and three diacids of different chain length (succinic acid, azelaic acid, and sebacic acid). All the polyesters obtained have a bio‐based content of 100% and number average molecular weight in the range of 28,000–116,000 Da. These average molecular weights are about 5–10 times higher than those of most reported aliphatic polyesters synthesized through similar reaction routes but at temperatures > 230°C. The over‐heating phenomenon, i.e., the observation of thermal degradation behavior of these polyesters at 230°C is reported. The crystallization behavior, mechanical properties, and enzymatic hydrolysis rate of the polyesters obtained are characterized. Poly(butylene succinate) (PBSu) shows the highest crystallinity and melting temperature, but the lowest thermal stability and slowest potential rate of enzymatic biodegradation rate compared with poly(butylene azelate) and poly(butylene sebacate). © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40579.
Structural characterization of hydrophilic polymer blends/montmorillonite clay nanocomposites
Authors: Sengwa Ram Jeewan , Choudhary Shobhna
Published: March 2014

The nanocomposite films comprising polymer blends of poly(vinyl alcohol) (PVA), poly(vinyl pyrrolidone) (PVP), poly(ethylene oxide) (PEO), and poly(ethylene glycol) (PEG) with montmorillonite (MMT) clay as nanofiller were prepared by aqueous solution casting method. The X‐ray diffraction studies of the PVA–x wt % MMT, (PVA–PVP)–x wt % MMT, (PVA–PEO)–x wt % MMT and (PVA–PEG)–x wt % MMT nanocomposites containing MMT concentrations x = 1, 2, 3, 5 and 10 wt % of the polymer weight were carried out in the angular range (2θ) of 3.8–30°. The values of MMT basal spacing d001, expansion of clay gallery width Wcg, d‐spacing of polymer spherulite, crystallite size L and diffraction peak intensity I were determined for these nanocomposites. The values of structural parameters reveal that the linear chain PEO and PEG in the PVA blend based nanocomposites promote the amount of MMT intercalated structures, and these structures are found relatively higher for the (PVA–PEO)–x wt % MMT nanocomposites. It is observed that the presence of bulky ester‐side group in PVP backbone restricts its intercalation, whereas the adsorption behavior of PVP on the MMT nanosheets mainly results the MMT exfoliated structures in the (PVA–PVP)–x wt % MMT nanocomposites. The crystallinities of the PEO and PEG were found low due to their blending with PVA, which further decreased anomalously with the increase of MMT concentration in the nanocomposites. The decrease of polymer crystalline phase of these materials confirmed their suitability in preparation of novel solid polymer nanocomposite electrolytes. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40617.
Electrocyclic Reactions of Siloles: A Combined Experimental and Theoretical Study
Authors: Meyer‐Wegner Frank , Wender Josef H. , Falahati Konstantin , Porsch Timo , Sinke Tanja , Bolte Michael , Wagner Matthias , Holthausen Max C. , Lerner Hans‐Wolfram
Published: March 2014

The reaction of 4‐chloro‐1,2‐dimethyl‐4‐supersilylsila‐1‐cyclopentene (2 a) with Li[NiPr2] at −78 °C results in the formation of the formal 1,4‐addition product of the silacyclopentadiene derivative 3,4‐dimethyl‐1‐supersilylsila‐1,3‐cyclopentadiene (4 a) with 2,3‐dimethyl‐4‐supersilylsila‐1,3‐cyclopentadiene (5 a). In addition the respective adducts of the Diels–Alder reactions of 4 a+4 a and 4 a+5 a were obtained. Compound 4 a, which displays an s‐cis‐silacyclopentadiene configuration, reacts with cyclohexene to form the racemate of the [4+2] cycloadduct of 4 a and cyclohexene (9). In the reaction between 4 a and 2,3‐dimethylbutadiene, however, 4 a acted as silene as well as silacyclopentadiene to yield the [2+4] and [4+2] cycloadducts 10 and 11, respectively. The constitutions of 9, 10, and 11 were confirmed by NMR spectroscopy and their crystal structures were determined. Reaction of 4‐chloro‐1,2‐dimethyl‐4‐tert‐butyl‐4‐silacyclopent‐1‐ene (2 c) with KC8 yielded the corresponding disilane (12), which was characterized by X‐ray crystal structure analysis (triclinic, P$\bar 1$). DFT calculations are used to unveil the mechanistic scenario underlying the observed reactivity.
Thermal‐Induced Formation of a Three‐Dimensional Nanoplasmonic Sensor from Ag Nanocubes with High Stability and Reusability
Authors: Lu Weiwei , Song Yingli , Yao Kaisheng , Wang Jianji
Published: March 2014

Nanoplasmonic sensors based on the localized surface plasmon resonance (LSPR) of noble metal nanoparticles have many advantages, such as real‐time detection, no need for reagent labelling, and no use of complicated equipment. However, the nanoplasmonic sensors with two dimensional structures usually suffer from a low LSPR signal and thus low sensitivity due to the low density of the nanoparticles. In addition, complicated surface functionalization is always required to suppress the non‐specific binding of the analyst to the substrate of the sensor, because the two types of surface, that is, metal and substrate surfaces, are simultaneously exposed to the reaction medium. To overcome these problems, an innovative thermal‐induced method has been proposed in the present work, to construct three dimensional (3D) nanostructure of Ag nanocubes on both surfaces of the substrate by using the unique amphiphilic property of 2‐diethylaminoethanethiol. The prepared nanoplasmonic sensor is highly sensitive due to the high density of 3D structure of the nanoparticles and the low non‐specific binding since only one type of surface is exposed. To enhance the stability of the sensor, a thin SiO2 overlayer was formed on the surface without using an additional coupling agent. Furthermore, the NiII‐nitriloacetic acid (NiII‐NTA) complex was covalently bound on the surface, so that the regeneration and reuse of the sensor becomes easy. Therefore, the easy fabrication, high stability, and good reusability of this 3D LSPR sensor makes our method competitive for the development of nanoplasmonic sensors.
A One‐Pot O‐Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α‐(Phosphinyloxy)amide Derivatives
Authors: Soeta Takahiro , Matsuzaki Syunsuke , Ukaji Yutaka
Published: March 2014

A one‐pot O‐phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding α‐(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini‐type, isocyanide‐based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity of the phosphinate group allows a subsequent catalytic Pudovik‐type reaction, affording the highly functionalized α‐(phosphinyloxy)amide derivative in high yield. A wide range of aldehydes and isocyanides are applicable to this reaction.
Chemical Synthesis of Asparagine‐Linked Archaeal N‐Glycan from Methanothermus fervidus
Authors: Sanapala Someswara Rao , Kulkarni Suvarn S.
Published: March 2014

Several N‐linked glycoproteins have been identified in archaea and there is growing evidence that the N‐glycan is involved in survival and functioning of archaea in extreme conditions. Chemical synthesis of the archaeal N‐glycans represents a crucial step towards understanding the putative function of protein glycosylation in archaea. Herein the first total synthesis of the archaeal L‐asparagine linked hexasaccharide from Methanothermus fervidus is reported using a highly convergent [3+3] glycosylation approach in high overall yields. The synthesis relies on efficient preparation of regioselectively protected thioglycoside building blocks for orthogonal glycosylations and late stage N‐aspartylation.
On the Role of Pre‐ and Post‐Electron‐Transfer Steps in the SmI2/Amine/H2O‐Mediated Reduction of Esters: New Mechanistic Insights and Kinetic Studies
Authors: Szostak Michal , Spain Malcolm , Procter David J.
Published: March 2014

The mechanism of the SmI2‐mediated reduction of unactivated esters has been studied using a combination of kinetic, radical clocks and reactivity experiments. The kinetic data indicate that all reaction components (SmI2, amine, H2O) are involved in the rate equation and that electron transfer is facilitated by Brønsted base assisted deprotonation of water in the transition state. The use of validated cyclopropyl‐containing radical clocks demonstrates that the reaction occurs via fast, reversible first electron transfer, and that the electron transfer from simple Sm(II) complexes to aliphatic esters is rapid. Notably, the mechanistic details presented herein indicate that complexation between SmI2, H2O and amines affords a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to carboxylic acid derivatives as an attractive alternative to the classical hydride‐mediated reductions and as a source of acyl‐radical equivalents for CC bond forming processes.
Chirality in the Absence of Rigid Stereogenic Elements: Steric and Electronic Effects on the Configurational Stability of C3 Symmetric Residual Tris‐Aryl Phosphanes
Authors: Rizzo Simona , Cirilli Roberto , Pierini Marco
Published: March 2014

Residual stereoisomers result whenever closed subsets of appropriately substituted interconverting isomers (the residual stereoisomers) are generated from a full set of stereoisomers under the operation of a favored stereomerization mechanism. In the case of the three‐bladed propellers, differentiation of the edges of the blades and strict correlation in the motion of the rings are the prerequisites for the existence of residual stereoisomers. In these systems, the two‐ring flip mechanism is the lowest energy process. It does not interconvert all possible conformational stereoisomers generated by helicity and the three‐blade‐hub rotors. In the case of C3 symmetric systems, two noninterconverting subgroups (the residual stereoisomers) are generated, each one constituted of quickly interconverting diastereoisomers. A series of tris‐aryl phosphanes, structurally designed for existing as residual enantiomers or diastereoisomers, bearing substituents differing in size and electronic properties on the aryl rings, were synthesized and characterized. The configurational stability of residual phosphanes, evaluated by dynamic 1H‐ and 31P‐NMR analysis and by dynamic enantioselective high‐performance liquid chromatography (HPLC), was found 10 kcal mol‐1 lower than that shown by the corresponding phosphane‐oxides. In accordance with the calculations, an unexpectedly low barrier for phosphorus pyramidal inversion was invoked as responsible for the scarce configurational stability of the residual tris‐arylphosphanes. Chirality 26:601–606, 2014. © 2014 Wiley Periodicals, Inc.
Comprehensive Chiroptical Study of Proline‐Containing Diamide Compounds
Authors: Knapp Krisztina , Górecki Marcin , Frelek Jadwiga , Luboradzki Roman , Hollósi Miklós , Majer Zsuzsa , Vass Elemér
Published: March 2014

The continuously growing interest in the understanding of peptide folding led to the conformational investigation of methylamides of N‐acetyl‐amino acids as diamide models. Here we report the results of detailed conformational analysis on Ac‐Pro‐NHMe and Ac‐β‐HPro‐NHMe diamides. These compounds were analyzed by experimental and computational methods, the conformational distributions obtained by Density Functional Theory (DFT) calculations for isolated and solvated diamide compounds are discussed. The conformational preference of proline‐containing diamide compounds as a function of the ambience was observed by a number of chiroptical spectroscopic techniques, such as vibrational circular dichroism (VCD), electronic circular dichroism (ECD), Raman optical activity (ROA) spectroscopy, and additionally by single crystal X‐ray diffraction analyses. Based on a comparison between Ac‐Pro‐NHMe and Ac‐β‐HPro‐NHMe, one can conclude that due to the greater conformational freedom of the β‐HPro derivative, Ac‐β‐HPro‐NHMe shows different behavior in solid‐ and solution‐phase, as well. Ac‐β‐HPro‐NHMe tends to form cis Ac‐β‐HPro amide conformation in water, dichloromethane, and acetonitrile in contrast to its α‐Pro analog. On the other hand, the crystal structure of the β‐HPro compound cannot be related to any of the conformers obtained in vacuum and solution while the X‐ray structure of Ac‐Pro‐NHMe was identified as tαL–, which is a trans Ac‐Pro amide containing conformer also predominant in polar solvents. Chirality 26:228–242, 2014. © 2014 Wiley Periodicals, Inc.
N‐H Stretching Modes Around 3300 Wavenumber From Peptide Backbones Observed by Chiral Sum Frequency Generation Vibrational Spectroscopy
Authors: Fu Li , Wang Zhuguang , Yan Elsa C. Y.
Published: March 2014

We present a detailed analysis of the molecular origin of the chiral sum frequency generation (SFG) signals of proteins and peptides at interfaces in the N‐H stretching vibrational region. The N‐H stretching can be a probe for investigating structural and functional properties of proteins, but remains technically difficult to analyze due to the overlapping with the O‐H stretching of water molecules. Chiral SFG spectroscopy offers unique tools to study the N‐H stretching from proteins at interfaces without interference from the water background. However, the molecular origin of the N‐H stretching signals of proteins is still unclear. This work provides a justification of the origin of chiral N‐H signals by analyzing the vibrational frequencies, examining chiral SFG theory, studying proton (hydrogen/deuterium) exchange kinetics, and performing optical control experiments. The results demonstrate that the chiral N‐H stretching signals at ~3300 cm‐1 originate from the amide group of the protein backbones. This chiral N‐H stretching signal offers an in situ, real‐time, and background‐free probe for interrogating the protein structures and dynamics at interfaces at the molecular level. Chirality 26:521–524, 2014. © 2014 Wiley Periodicals, Inc.
Targeting Cystalysin, a Virulence Factor of Treponema denticola‐Supported Periodontitis
Authors: Spyrakis Francesca , Cellini Barbara , Bruno Stefano , Benedetti Paolo , Carosati Emanuele , Cruciani Gabriele , Micheli Fabrizio , Felici Antonio , Cozzini Pietro , Kellogg Glen E. , Voltattorni Carla Borri , Mozzarelli Andrea
Published: March 2014

Cystalysin from Treponema denticola is a pyridoxal 5′‐phosphate dependent lyase that catalyzes the formation of pyruvate, ammonia, and sulfide from cysteine. It is a virulence factor in adult periodontitis because its reaction contributes to hemolysis, which sustains the pathogen. Therefore, it was proposed as a potential antimicrobial target. To identify specific inhibitors by structure‐based in silico methods, we first validated the crystal structure of cystalysin as a reliable starting point for the design of ligands. By using single‐crystal absorption microspectrophotometry, we found that the enzyme in the crystalline state, with respect to that in solution, exhibits: 1) the same absorption spectra for the catalytic intermediates, 2) a close pKa value for the residue controlling the keto enamine ionization, and 3) similar reactivity with glycine, L‐serine, L‐methionine, and the nonspecific irreversible inhibitor aminoethoxyvinylglycine. Next, we screened in silico a library of 9357 compounds with the Fingerprints for Ligands and Proteins (FLAP) software, by using the three‐dimensional structure of cystalysin as a template. From the library, 17 compounds were selected and experimentally evaluated by enzyme assays and spectroscopic methods. Two compounds were found to competitively inhibit recombinant T. denticola cystalysin, with inhibition constant (Ki) values of 25 and 37 μM. One of them exhibited a minimum inhibitory concentration (MIC) value of 64 μg mL−1 on Moraxella catarrhalis ATCC 23246, which proves its ability to cross bacterial membranes.
Pig models of neurodegenerative disorders: Utilization in cell replacement‐based preclinical safety and efficacy studies
Authors: Dolezalova Dasa , Hruska‐Plochan Marian , Bjarkam Carsten R. , Sørensen Jens Christian H. , Cunningham Miles , Weingarten David , Ciacci Joseph D. , Juhas Stefan , Juhasova Jana , Motlik Jan , Hefferan Michael P. , Hazel Tom , Johe Karl , Carromeu Cassiano , Muotri Alysson , Bui Jack , Strnadel Jan , Marsala Martin
Published: March 2014

An important component for successful translation of cell replacement‐based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large‐scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naïve noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed. J. Comp. Neurol. 522:2784–2801, 2014. © 2014 Wiley Periodicals, Inc.