bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of redox homeostasis for combinatorial drug efficacy in K-Ras tumors as revealed by metabolic connectivity profiling
Authors: Gaglio Daniela , Bonanomi Marcella , Valtorta Silvia , Bharat Rohit , Ripamonti Marilena , Conte Federica , Fiscon Giulia , Righi Nicole , Napodano Elisabetta , Papa Federico , Raccagni Isabella , Parker Seth J. , Cifola Ingrid , Camboni Tania , Paci Paola , Colangelo Anna Maria , Vanoni Marco , Metallo Christian M. , Moresco Rosa Maria , Alberghina Lilia
Published: September 2020

Background

Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways.

Methods

We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity.

Results

We show that K-Ras-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NVP-BKM120 more consistently reduces cell growth of tumor xenografts. Maximal growth inhibition correlates with the disruption of redox homeostasis, involving loss of reduced glutathione regeneration, redox cofactors, and a decreased connectivity among metabolites primarily involved in nucleic acid metabolism.

Conclusions

Our findings open the way to develop metabolic connectivity profiling as a tool for a selective strategy of combined drug repositioning in precision oncology.
Roles of IFN-γ in tumor progression and regression: a review
Authors: Jorgovanovic Dragica , Song Mengjia , Wang Liping , Zhang Yi
Published: September 2020

Background

Interferon-γ (IFN-γ) plays a key role in activation of cellular immunity and subsequently, stimulation of antitumor immune-response. Based on its cytostatic, pro-apoptotic and antiproliferative functions, IFN-γ is considered potentially useful for adjuvant immunotherapy for different types of cancer. Moreover, it IFN-γ may inhibit angiogenesis in tumor tissue, induce regulatory T-cell apoptosis, and/or stimulate the activity of M1 proinflammatory macrophages to overcome tumor progression. However, the current understanding of the roles of IFN-γ in the tumor microenvironment (TME) may be misleading in terms of its clinical application.

Main body

Some researchers believe it has anti-tumorigenic properties, while others suggest that it contributes to tumor growth and progression. In our recent work, we have shown that concentration of IFN-γ in the TME determines its function. Further, it was reported that tumors treated with low-dose IFN-γ acquired metastatic properties while those infused with high dose led to tumor regression. Pro-tumorigenic role may be described through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, upregulation of indoleamine 2,3-dioxygenase, and checkpoint inhibitors such as programmed cell death ligand 1.

Conclusion

Significant research efforts are required to decipher IFN-γ-dependent pro- and anti-tumorigenic effects. This review discusses the current knowledge concerning the roles of IFN-γ in the TME as a part of the complex immune response to cancer and highlights the importance of identifying IFN-γ responsive patients to improve their sensitivity to immuno-therapies.
Radioulnar joint reconstruction: a novel surgical technique and biomechanical assessment for chronic instability
Authors: Ferreira Gustavo Pacheco Martins , Simões Marcella Rodrigues Costa , de Freitas Junior Haroldo Oliveira , de Castro Ubiratan Brum , Pires Robinson Esteves , de Andrade Marco Antonio Percope
Published: September 2020

Purpose

This study aims to describe and biomechanically evaluate a novel technique using a strip of the flexor carpi ulnaris tendon for distal radioulnar joint reconstruction.

Methods

Surgical technique was thoroughly detailed, and a cadaveric biomechanical test was conducted to evaluate sagittal plane stability. Pronosupination range of motion was measured before and after the procedure. Dorsal and volar translation resistances were checked in three situations: with the uninjured triangular fibrocartilage complex, after its complete resection and after the surgical procedure.

Results

For distal radioulnar joint translation, higher values were found both in dorsal and volar translation in situations with an injured triangular fibrocartilage complex, with means equal to 25.4 mm (SD: 9.4 mm) and 26.1 mm (SD: 8.0 mm), respectively. For intact triangular fibrocartilage complex, both dorsal and volar translations averages were 3.4 mm (SD: 0.9 mm) and 4.5 mm (SD: 1.8 mm), respectively. Finally, when evaluating dorsal and volar translations after surgical reconstruction, means were 6.3 mm (SD: 1.3 mm) and 6.8 mm (SD: 0.9 mm), respectively. Regarding supination and pronation range of motion, which ranged from 57.9 to 63.4o, there were no differences in mean and median measures, when the cadavers with intact and reconstructed triangular fibrocartilage complex were compared (p > 0.05).

Conclusion

Promising mechanical evaluations encourage us to hypothesize that the technique effectively reconstructs the dorsal and volar radioulnar ligaments, preserving pronosupination and maintaining the physiological characteristics of the wrist joint. Clinical comparative studies are still necessary to fully validate this procedure.

Level of evidence

Therapeutic - Level V.
Development and evaluation of an automated quantification tool for amyloid PET images
Authors: Tsubaki Yuma , Akamatsu Go , Shimokawa Natsumi , Katsube Suguru , Takashima Aya , Sasaki Masayuki ,   Japanese Alzheimer’s Disease Neuroimaging Initiative
Published: September 2020

Background

Quantitative evaluation of amyloid positron emission tomography (PET) with standardized uptake value ratio (SUVR) plays a key role in clinical studies of Alzheimer’s disease (AD). We have proposed a PET-only (MR-free) amyloid quantification method, although some commercial software packages are required. The aim of this study was to develop an automated quantification tool for amyloid PET without using commercial software.

Methods

The quantification tool was created by combining four components: (1) anatomical standardization to positive and negative templates using NEUROSTAT stereo.exe; (2) similarity calculation between standardized images and respective templates based on normalized cross-correlation (selection of the image for SUVR measurement); (3) voxel value normalization by the mean value of reference regions (making an SUVR-scaled image); and (4) SUVR calculation based on pre-defined regions of interest (ROIs). We examined 166 subjects who underwent a [11C] Pittsburgh compound-B PET scan through the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) study. SUVRs in five ROIs (frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate cortex and precuneus) were calculated with the cerebellar cortex as the reference region. The SUVRs obtained by our tool were compared with manual step-by-step processing and the conventional PMOD-based method (PMOD Technologies, Switzerland).

Results

Compared with manual step-by-step processing, our developed automated quantification tool reduced processing time by 85%. The SUVRs obtained by the developed quantification tool were consistent with those obtained by manual processing. Compared with the conventional PMOD-based method, the developed quantification tool provided 1.5% lower SUVR values, on average. We determined that this bias is likely due to the difference in anatomical standardization methods.

Conclusions

We developed an automated quantification tool for amyloid PET images. Using this tool, SUVR values can be quickly measured without individual MRI and without commercial software. This quantification tool may be useful for clinical studies of AD.
New records of Leopardus guigna in its northern-most distribution in Chile: implications for conservation
Authors: Napolitano Constanza , Larraguibel-González Cristian , Cepeda-Mercado Amancay A. , Vial Pablo , Sanderson Jim
Published: September 2020

We report new records of the wild felid Leopardus guigna in its northern-most distribution, in the southern Coquimbo and northern Valparaíso regions, in northern-central Chile. To our knowledge, these are the northern-most confirmed guigna records to date. We discuss implications for the conservation of these fragile populations in the face of different anthropic threats.
The adaptive immune response in cardiac arrest resuscitation induced ischemia reperfusion renal injury
Authors: Tsivilika Maria , Doumaki Eleni , Stavrou George , Sioga Antonia , Grosomanidis Vasilis , Meditskou Soultana , Maranginos Athanasios , Tsivilika Despina , Stafylarakis Dimitrios , Kotzampassi Katerina , Papamitsou Theodora
Published: September 2020

Background

The present study aims to investigate, immunohistochemically, the role of the adaptive immune response in cardiac arrest/resuscitation-induced ischemia–reperfusion renal injury (IRI), namely to assess the presence of lymphocytes in renal tissue samples and the connection between the extent of the damage and the concentration of the lymphocytes by comparing the kidneys of non resuscitated swine with the kidneys of resuscitated swine.

Methods

Twenty four swine underwent cardiac arrest (CA) via a pacemaker wire. After 7 min, without any intervention, Cardiopulmonary Resuscitation, CPR, was commenced. Five min after CPR was commenced advanced life-support, ALS. Animals were divided into resuscitated animals and non resuscitated animals. Tissue samples obtained from the two groups for immunohistological study aiming to detect T-cells, B-cells and plasma cells using CD3 + , CD20 + , and CD138 + antibodies.

Results

There seems to be a strong concentration of T lymphocytes in the kidney tissues after ischemia of both non-resuscitated and resuscitated swine. B lymphocytes, also, appear to have infiltrated the ischemic kidneys of both animal groups; nevertheless, the contribution of T lymphocytes to the induction of injury remains greater. There is no strong evidence of correlation between the plasma cells and the damage.

Conclusion

The adaptive immune response seems to have a strong association with kidney injury and acute tubular necrosis after cardiac arrest/ resuscitation-induced ischemia–reperfusion. However, the extent to which the adaptive immune cells are involved in the induction of renal injury remains uncertain and there are many questions about the mechanism of function of these cells, the answers of which require further studies.
Hepatic resection for recurrent hepatocellular carcinoma during pregnancy: a case report
Authors: Maeda Takashi , Imai Daisuke , Wang Huanlin , Yugawa Kyohei , Kinjo Nao , Kawata Koto , Ikeda Shinichiro , Edahiro Keitaro , Takeishi Kazuki , Iguchi Tomohiro , Kayashima Hiroto , Harada Noboru , Ninomiya Mizuki , Yamaguchi Shohei , Konishi Kozo , Tsutsui Shinichi , Matsuda Hiroyuki
Published: September 2020

Background

Hepatocellular carcinoma (HCC) during pregnancy is extremely rare. Treatment strategies for cancers detected during pregnancy have been controversial. We herein report a case of recurrent HCC detected at 20 weeks of pregnancy, which subsequently prompted hepatic resection after abortion.

Case presentation

A 36-year-old woman underwent laparoscopic partial hepatectomy for HCC (20 mm in diameter) in segment 5 of the liver during follow-up after being determined as a hepatitis B virus carrier two and a half years ago. Post-surgery follow-up abdominal ultrasonography revealed a 36-mm tumor in segment 7 of the liver. Abdominal contrast-enhanced computed tomography revealed a well-enhanced tumor with a 40-mm diameter in segment 7 adjacent to the inferior vena cava and right hepatic vein, suggesting HCC recurrence. Laboratory data revealed total bilirubin (0.4 mg/dL), aspartate aminotransferase (28 IU/L), alanine aminotransferase (30 IU/L), glutamyltransferase (16 IU/L), prothrombin time (115.3%), and indocyanine green retention rate at 15 min (7.0%). α-Fetoprotein (AFP) (12,371.5 ng/mL; normal range < 10 ng/mL) and PIVKA-II (208 mAU/mL; normal range < 40 mAU/mL) were both significantly elevated. After discussions with a cancer board consisting of experts from the departments of gastroenterology, obstetrics and gynecology, and surgery, as well as obtaining appropriate informed consent from the patient and her family, we decided to perform a hepatic resection after abortion. Subsequently, abortion surgery was performed at 21 weeks and 2 days of pregnancy. After 6 days, subsegmentectomy of liver segment 7 was performed under general and epidural anesthesia, with a pathological diagnosis which was moderately differentiated HCC being established. Given the good postoperative course, without particular complications, the patient was subsequently discharged 10 days after the operation. Approximately 2 years after the surgery, the patient remains alive without recurrence, while both AFP and PIVKA-II were within normal limits.

Conclusions

Treatment strategies for HCC detected during pregnancy remain controversial. As such, decisions should be made based on HCC growth and fetal maturity after thorough multidisciplinary team discussions and obtaining appropriate informed consent from the patient and her family.
Adult intussusception secondary to an appendiceal tumour in a patient with ulcerative colitis: a case report
Authors: Davey M. G. , Conlon E. T. , Forde G. , Byrnes V. M. , Carroll P. A.
Published: September 2020

Background

Intussusception in adult patients is uncommon and appendiceal lead points are particularly rare.

Case presentation

We present the case of a 42-year-old male with a history of ulcerative colitis, presenting with sudden onset abdominal pain and bloody diarrhoea. Endoscopy revealed grossly normal mucosa in the descending colon with a congested polypoid mass in the proximal transverse colon. Computed tomography revealed ileocecal intussusception at the hepatic flexure. A right hemicolectomy was performed, where a grossly dilated appendix was noted, resected and sent for histopathological evaluation. Results revealed low-grade appendiceal mucinous neoplasm. Post-operatively, the patient remained symptom free, however required reintroduction of biologic therapy due to relapse of his ulcerative colitis 12 weeks later.

Conclusion

This case depicts a rare acute surgical presentation and reminds physicians and surgeons of the importance of ‘thinking outside the box’ in clinical practice.
Strategies for immune regulation in iPS cell-based cardiac regenerative medicine
Authors: Murata Kozue , Ikegawa Masaya , Minatoya Kenji , Masumoto Hidetoshi
Published: September 2020

Cardiac regenerative therapy is expected to be a promising therapeutic option for the treatment of severe cardiovascular diseases. Artificial tissues or organoids made from cardiovascular cell lineages differentiated from human induced pluripotent stem cells (iPSCs) are expected to regenerate the damaged heart. Even though immune rejection rarely occurs when iPSC-derived graft and the recipient have the same HLA type, in some cases, such as tissue transplantation onto hearts, the HLA matching would not be sufficient to fully control immune rejection. The present review introduces recent immunomodulatory strategies in iPSC-based transplantation therapies other than MHC matching including the induction of immune tolerance through iPSC-derived antigen-presenting cells, simultaneous transplantation of syngeneic mesenchymal stem cells, and using the universal donor cells such as gene editing-based HLA modulation in iPSCs to regulate T cell compatibility. In addition, we present future perspectives for proper adjustment of immunosuppression therapy after iPSC-derived tissue/organoid-based cardiac regenerative therapies by identifying biomarkers monitoring immune rejection.
A model of cognitive evaluation battery for diagnosis of mild cognitive impairment and dementia in educated and illiterate Egyptian elderly people
Authors: ElKholy Nehal , Tawfik Heba Mohamed , Ebeid Somaia , Madkor Omaima Refat Elsayed , Hamza Sarah Ahmed
Published: September 2020

Background

The high illiteracy rates in the North African and Middle Eastern region make direct cognitive testing challenging. Validated instruments for dementia in Arabic language are lacking specially those targeting low-educated subjects.

Objectives

The aim of this study was to develop a cognitive evaluation battery suitable for both educated and illiterate Egyptian elderly people.

Design

A cross-sectional study was conducted. Setting: Ain-Shams University geriatric and ophthalmology wards, geriatrics outpatient clinic, and geriatric clubs. Participants: 159 male and female participants aged ≥ 60 years were recruited.

Measurements

Cut-off points were determined according to DSM-IV criteria for dementia and MMSE scores which divided the participants into 3 quadrants as normal, having mild cognitive impairment and having dementia then application of the new battery test was done.

Results

Test re-test reliability ranged from adequate to high in most of its tests with r ≥ 0.7. There was a statistical significance between all battery tests when divided into normal and dementia according to DSM IV criteria except in digit span forward length, digit span backward length, stimulus cue of confrontation naming and judgment. Means and standard deviations were calculated for each battery subset, for the whole sample, for low-educated group and group with > 9 years education according to three quadrants of MMSE.

Conclusion

A new valid and reliable neurocognitive evaluation battery that can differentiate between normal, mild cognitive impairment, and dementia in both educated and illiterate subjects under the name of Ain Shams Cognitive Assessment (ASCA) scale is now available.
Effect of mirror therapy on hand functions in Egyptian chronic stroke patients
Authors: Shaker Hussein , Fahmy Ebtesam Mohammed , Honin Ayman Anwar Nassif , Mohamed Shaimaa Shaheen
Published: September 2020

Background

Most stroke survivors (more than 60%) suffer from persistent neurological impairments that significantly affect activities of daily living. Hand functions are essential for doing daily living and working activities. Mirror therapy is shown to be effective in improving hand functional recovery in stroke patients.

Objective

This study aimed to determine the effect of mirror therapy on improving hand functions in Egyptian chronic stroke patients.

Subjects and methods

Thirty chronic ischemic stroke patients from both sexes participated in the study. Their ages ranged from 45 to 65 years. They were randomly assigned into two equal groups: the study group that received a selected physical therapy program in addition to the mirror therapy and the control group that received the same selected physical therapy program but without a mirror therapy. Treatment sessions were conducted three times per week for 8 weeks. Range of motion (ROM) of the wrist extension and forearm supination, hand grip strength, and the time of Jebson Hand Function Test (JHFT) were measured before and after the treatment program.

Results

There were statistically significant increases in the range of motion of the wrist extension and forearm supination and hand grip strength with a decrease in the time of Jebson Hand Function Test in both groups post-treatment. Post-treatment improvement was more significant in the study group compared to the control group.

Conclusion

Mirror therapy had a positive effect on improving hand motor functional skills in a sample of Egyptian chronic stroke patients.
Influence of sulfide, chloride and dissolved organic matter on mercury adsorption by activated carbon in aqueous system
Authors: Chen Chi , Ting Yu , Ch’ng Boon-Lek , Hsi Hsing-Cheng
Published: September 2020

Using activated carbon (AC) as thin layer capping to reduce mercury (Hg) released from contaminated sediment is a feasible and durable remediation approach. However, several aqueous factors could greatly affect the Hg fate in the aquatic system. This study thus intends to clarify the influences on Hg adsorption by AC with the presence of sulfide, dissolved organic matter (DOM), and chloride. The lab-scale batch experiments were divided into two parts, including understanding (1) AC adsorption performance and (2) Hg distribution in different phases by operational definition method. Results showed that the Hg adsorption rate by AC was various with the presence of sulfide, chloride, and DOM (from fast to slow). Hg adsorption might be directly bonded to AC with Hg-Cl and Hg-DOM complexes and the rate was mainly controlled by intraparticle diffusion. In contrast, “Hg + sulfide” result was better described by pseudo-second order kinetics. The Hg removal efficiency was 92–95% with the presence of 0–400 mM chloride and approximately 65–75% in the “Hg + sulfide” condition. Among the removed Hg, 24–29% was formed into aqueous-phase particles and about 30% Hg was adsorbed on AC with 2–20 μM sulfide. Increasing DOM concentration resulted in more dissolved Hg. The proportion of dissolved Hg increased 31% by increasing DOM concentration from 0.25 to 20 mg C L− 1. Simultaneously, the proportion of adsorbed Hg by AC decreased by 47%. Overall, the presence of chloride increases the Hg adsorption by AC. In contrast, the presence of sulfide and DOM causes a negative effect on AC adsorption.
Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure
Authors: Metwally Yasser Gaber , Sedrak Heba Kamal , Shaltout Inass Fahiem
Published: September 2020

Background

Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR).

So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure.

Results

Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively).

Conclusion

Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.
Comparison of isolated venous approach with the standard approach in children undergoing patent ductus arteriosus device closure
Authors: Uppal Lipi , Rohit Manoj Kumar , Barwad Parag , Naganur Sanjeev , Debi Uma , Kasinadhuni Ganesh , Santosh Krishna , CR Pruthvi , Sahoo Saroj
Published: September 2020

Background

Transcatheter device closure is a safe procedure recommended in children with patent ductus arteriosus (PDA). While the standard procedure uses arterial and venous femoral access, it poses risk of vascular complications especially in young infants. Isolated venous approach has been tried in a few studies and was found to be non-inferior to the standard technique. In this prospective observational study, we have compared the two vascular approaches of PDA device closure in pediatric patients and have also studied the feasibility of this approach in young children with weight < 6 kg.

Results

PDA device occlusion was performed with either one of the approaches—venous alone (group I) or standard approach (group II) in a total of 135 children enrolled prospectively. The baseline data, procedural outcomes, vascular complications, and radiation dose were compared between the two groups.

Fifty-two and 83 children were included in group I and group II, respectively. A total of 22 children (16%) (13 in group I; 9 in group II) had weight < 6 kg. In group II, 6 children (7.2%) had vascular site complications treated with heparin infusion with two children requiring thrombolysis. Another child in group II developed intravascular hemolysis following residual shunt, requiring surgical device retrieval and closure. No significant differences were observed in mean fluoroscopic time (p= 0.472) and air kerma between the two groups (p= 0.989).

Conclusion

Transcatheter PDA device closure without arterial access is a feasible and safe option in children including young infants. This technique avoids the risk of vascular complications although requires careful case selection.
Metabolite Signature of Albuminuria Involves Amino Acid Pathways in 8661 Finnish Men Without Diabetes
Authors: Fernandes Silva Lilian , Vangipurapu Jagadish , Smith Ulf , Laakso Markku
Published: September 2020

Objective

To investigate the metabolite signature of albuminuria in individuals without diabetes or chronic kidney disease to identify possible mechanisms that result in increased albuminuria and elevated risk of type 2 diabetes (T2D).

Research Design and Methods

The study cohort was a population-based Metabolic Syndrome In Men (METSIM) study including 8861 middle-aged and elderly Finnish men without diabetes or chronic kidney disease at baseline. A total of 5504 men participated in a 7.5-year follow-up study, and 5181 of them had metabolomics data measured by Metabolon’s ultrahigh performance liquid chromatography-tandem mass spectroscopy.

Results

We found 32 metabolites significantly (P < 5.8 × 10-5) and positively associated with the urinary albumin excretion (UAE) rate. These metabolites were especially downstream metabolites in the amino acid metabolism pathways (threonine, phenylalanine, leucine, arginine). In our 7.5-year follow-up study, UAE was significantly associated with a 19% increase (hazard ratio 1.19; 95% confidence interval, 1.13–1.25) in the risk of T2D after the adjustment for confounding factors. Conversion to diabetes was more strongly associated with a decrease in insulin secretion than a decrease in insulin sensitivity.

Conclusions

Metabolic signature of UAE included multiple metabolites, especially from the amino acid metabolism pathways known to be associated with low-grade inflammation, and accumulation of reactive oxygen species that play an important role in the pathogenesis of UAE. These metabolites were primarily associated with an increase in UAE and were secondarily associated with a decrease in insulin secretion and insulin sensitivity, resulting in an increased risk of incident T2D.
Age-dependent degeneration of an identified adult leg motor neuron in a Drosophila SOD1 model of ALS
Authors: Agudelo Anthony , St. Amand Victoria , Grissom Lindsey , Lafond Danielle , Achilli Toni , Sahin Asli , Reenan Robert , Stilwell Geoff
Published: September 2020

Mutations in superoxide dismutase 1 (SOD1) cause familial Amyotrophic lateral sclerosis (ALS) in humans. ALS is a neurodegenerative disease characterized by progressive motor neuron loss leading to paralysis and inevitable death in affected individuals. Using a gene replacement strategy to introduce disease mutations into the orthologous Drosophila sod1 (dsod1) gene, Here, we characterize changes at the neuromuscular junction using longer lived dsod1 mutant adults. Homozygous dsod1H71Y/H71Y or dsod1null/null flies display progressive walking defects with paralysis of the 3rd metathoracic leg. In dissected legs, we assessed age-dependent changes in a single identified motor neuron (MN-I2) innervating the tibia levitator muscle. At adult eclosion, MN-I2 of dsod1H71Y/H71Y or sod1null/null flies is patterned similar to wild type flies indicating no readily apparent developmental defects. Over the course of 10 days post-eclosion, MN-I2 shows an overall reduction in arborization with bouton swelling and loss of the post-synaptic marker discs-large (dlg) in mutant dsod1 adults. In addition, increases in polyubiquitinated proteins correlate with the timing and extent of MN-I2 changes. Because similar phenotypes are observed between flies homozygous for either dsod1H71Y or dsod1null alleles, we conclude these NMJ changes are mainly associated with sod loss of function. Together these studies characterize age-related morphological and molecular changes associated with axonal retraction in a Drosophila model of ALS that recapitulate an important aspect of the human disease.
Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway
Authors: Vanyai Hannah K. , Prin Fabrice , Guillermin Oriane , Marzook Bishara , Boeing Stefan , Howson Alexander , Saunders Rebecca E. , Snoeks Thomas , Howell Michael , Mohun Timothy J. , Thompson Barry
Published: September 2020

The Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis. Here we investigate the function of the Hippo pathway during the development of cartilage, which forms the majority of the skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap/Taz double knockout impairs chondrocyte proliferation, whilst constitutively nuclear nls-YAP5SA accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, in vivo, cartilage-specific knockout of Yap/Taz does not prevent chondrocyte proliferation, differentiation, or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of nls-YAP5SA or knockout of Lats1/2 do not increase cartilage growth but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include Ctgf, Cyr61 and several matrix remodelling enzymes. Thus, YAP/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.
SPAs promote thermomorphogenesis via regulating the phyB-PIF4 module in Arabidopsis
Authors: Lee Sanghwa , Paik Inyup , Huq Enamul
Published: September 2020

High ambient temperature due to global warming has a profound influence on plant growth and development at all stages of life cycle. Plant response to high ambient temperature termed thermomorphogenesis is characterized by hypocotyl and petiole elongation, and hyponastic growth at seedling stage. However, the molecular mechanism of thermomorphogenesis is still rudimentary. Here, we show that a set of four SUPPRESSOR OF PHYA-105 (SPA) genes is required for thermomorphogenesis. Consistently, SPAs are necessary for global gene expression changes in response to high ambient temperature. SPA1 level is unaffected, while the thermosensor phyB is stabilized in the spaQ mutant at high ambient temperature. Furthermore, in the absence of four SPA genes, the pivotal transcription factor PIF4 fails to accumulate, indicating a role of SPAs in regulating the phyB-PIF4 module at high ambient temperature. SPA1 directly phosphorylates PIF4 in vitro, and a mutant SPA1 affecting the kinase activity fails to rescue the PIF4 level as well as the thermo-insensitive phenotype of spaQ, suggesting that the SPA1 kinase activity is necessary for thermomorphogenesis. Taken together, these data suggest that SPAs are new components that integrate light and temperature signaling via fine tuning the phyB-PIF4 module.
RET overactivation leads to concurrent Hirschsprung disease and intestinal ganglioneuromas
Authors: Nagy Nandor , Guyer Richard A. , Hotta Ryo , Zhang Dongcheng , Newgreen Donald F. , Halasy Viktoria , Kovacs Tamas , Goldstein Allan M.
Published: September 2020

Appropriately balanced RET signaling is of critical importance during embryonic neural crest cell migration, proliferation, and differentiation. RET deficiency, for example, leads to intestinal aganglionosis (Hirschsprung disease), while overactive RET can lead to multiple endocrine neoplasia (MEN) syndromes. Some RET mutations are associated with both intestinal aganglionosis and MEN-associated tumors. This seemingly paradoxical occurrence has led to speculation of a “Janus mutation” in RET that causes overactivation or impairment of RET activity depending on the cellular context. Using an intestinal catenary culture system to test the effects of GDNF-mediated RET activation, we demonstrate the concurrent development of distal colonic aganglionosis and intestinal ganglioneuromas. Interestingly, the tumors induced by GDNF stimulation contain enteric neuronal progenitors capable of reconstituting an enteric nervous system when transplanted into a normal developmental environment. These results suggest that a Janus mutation may not be required to explain co-existing Hirschsprung disease and MEN-associated tumors, but rather that RET overstimulation alone is enough to cause both phenotypes. The results also suggest that reprogramming tumor cells toward nonpathological fates may represent a possible therapeutic avenue for MEN-associated neoplasms.
Vps13 is required for timely removal of nurse cell corpses
Authors: Faber Anita I. E. , van der Zwaag Marianne , Schepers Hein , Eggens-Meijer Ellie , Kanon Bart , IJsebaart Carmen , Kuipers Jeroen , Giepmans Ben N.G. , Freire Raimundo , Grzeschik Nicola A. , Rabouille Catherine , Sibon Ody C. M.
Published: September 2020

Programmed cell death and consecutive removal of cellular remnants is essential for development. During late stages of Drosophila melanogaster oogenesis, the small somatic follicle cells that surround the large nurse cells, promote non-apoptotic nurse cell death, subsequently engulf them, and contribute to the timely removal of nurse cell corpses. Here we identify a role for Vps13 in the timely removal of nurse cell corpses downstream of developmental programmed cell death. Vps13 is an evolutionary conserved peripheral membrane protein associated with membrane contact sites and lipid transfer. Vps13 is expressed in late nurse cells and persistent nurse cell remnants are observed when Vps13 is depleted from nurse cells but not from follicle cells. Microscopic analysis revealed enrichment of Vps13 in close proximity to the plasma membrane and the endoplasmic reticulum in nurse cells undergoing degradation. Ultrastructural analysis uncovered the presence of an underlying Vps13-dependent membranous structure in close association with the plasma membrane. The newly identified structure and function suggests the presence of a Vps13-dependent process required for complete degradation of bulky remnants of dying cells.
Diverse epithelial cell populations contribute to regeneration of secretory units in injured salivary glands
Authors: Ninche Ninche , Kwak Mingyu , Ghazizadeh Soosan
Published: September 2020

Salivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types including acinar, ductal and myoepithelial cells that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show that de novo formation of acini involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells including myoepithelial and ductal cells that appear to dedifferentiate to a progenitor-like state before re-differentiation to acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.
Plant homeodomain proteins provide a mechanism for how leaves grow wide
Authors: Conklin Phillip A. , Johnston Robyn , Conlon Brianne R. , Shimizu Rena , Scanlon Michael J.
Published: September 2020

The mechanisms whereby leaf anlagen undergo proliferative growth and expansion to form wide, flat leaves are unclear. The maize gene NARROWSHEATH1 (NS1) is a WUSCHEL-related homeobox3 (WOX3) homolog expressed at the margins of leaf primordia, and is required for mediolateral outgrowth. To investigate the mechanisms of NS1 function, we used chromatin immunoprecipitation and laser-microdissection RNAseq of leaf primordial margins to identify gene targets bound and modulated by NS1. Microscopic analyses of cell division and gene expression in expanding leaves, and reverse genetic analyses of homologous NS1 target genes in Arabidopsis, reveal that NS1 controls mediolateral outgrowth by repression of a growth inhibitor and promotion of cell division at primordial leaf margins. Intriguingly, homologous WOX gene products are expressed in stem-cell organizing centers and traffic to adjoining cells to activate stem-cell identity non-autonomously. In contrast, WOX3/NS1 does not traffic, and stimulates cell divisions in the same cells where it is transcribed.
The Not-So-Hot Melting Pot: The Persistence of Outcomes for Descendants of the Age of Mass Migration
Authors: Ward Zachary
Published: September 2020

How persistent are economic gaps across ethnicities? The convergence of ethnic gaps through the third generation of immigrants is difficult to measure because few datasets include grandparental birthplace. I overcome this limitation with a new three-generational dataset that links immigrant grandfathers in 1880 to their grandsons in 1940. I find that the persistence of ethnic gaps in occupational income is 2.5 times stronger than predicted by a standard grandfather-grandson elasticity. While part of the discrepancy is due to measurement error attenuating the grandfather-grandson elasticity, mechanisms related to geography also partially explain the stronger persistence of ethnic occupational differentials. (JEL J15, J22, J31, J51)
Job Displacement, Family Dynamics, and Spousal Labor Supply
Authors: Halla Martin , Schmieder Julia , Weber Andrea
Published: September 2020

We study the effectiveness of intrahousehold insurance among married couples when the husband loses his job due to a mass layoff or plant closure. Empirical results based on Austrian administrative data show that husbands suffer persistent employment and earnings losses, while wives’ labor supply increases moderately due to extensive margin responses. Wives’ earnings gains recover only a tiny fraction of the household income loss, and in the short-term, public transfers and taxes are a more important form of insurance. We show that the presence of children in the household is a crucial determinant of the wives’ labor supply response. (JEL D13, J12, J16, J22, J31, J63)
Partisan Shocks and Financial Markets: Evidence from Close National Elections
Authors: Girardi Daniele
Published: September 2020

This paper estimates the effect of partisan electoral victories on stock and bond markets. We employ a regression-discontinuity-based event study in a sample of 758 worldwide post-1945 national elections, using existing data on parliamentary elections and newly collected data on presidential elections. Left-wing electoral victories cause significant and substantial short-term decreases in stock market valuations, while the response of sovereign bond markets is mostly muted. Stock market effects are stronger and more persistent in elections in which the left’s proposed economic policy is more radical and in developing economies. (JEL D72, G14, N20, N40, O16, O17)
Beyond our 20th year: what happens next?
Authors: Bueser Teofila ‘Tootie’
Published: September 2020

This month, Teofila ‘Tootie’ Bueser, Immediate Past President of the BANCC council, reflects on the history and future of the BANCC.
Thymomas in rabbits
Authors: Sibbald Rachel
Published: September 2020

This article will look at thymoma recognition and treatment in rabbits. Medical versus surgical treatment options will be explored along with nursing strategies for dyspnoeic rabbit patients. Thymomas are slow growing neoplasms in the cranial mediastinum that can pose life-threatening complications to rabbit patients. Although the incidence of this condition is thought to be low, clinicians and nurses should be aware of the symptoms and morbidity associated with this condition in order to provide rabbits with the correct treatment options.
Help to ensure that owners don't make this bonfire night a night to remember!
Authors: Hargrave Claire
Published: September 2020

The 2020 firework season will pose a huge welfare problem for many pets. Claire Hargrave explains how you can prepare owners of all companion animals for this noisy time of year.
"Weinen, Klagen, Sorgen, Zagen" und die antike Redekunst
Authors: Ambrose Z. Philip
Published: September 2020

Der Text von BWV 12, der offensichtlich von Bachs Weimarer Librettisten Samuel Franck verfasst wurde, wird hinsichtlich seiner rhetorischen Substanz und seiner spezifischen Beziehung zu einem Vers des römischen Dichters Quintus Ennius ("flentes, plorantes, lacrimantes, obtestantes") diskutiert. Zwischen dem Werk Francks und der Rhetorik der Antike ergibt sich eine Reihe von Verbindungen, die vermutlich auch für Bachs Verständnis der Franck'schen Kantatentexte von Bedeutung waren. (Übertragung des englischen Resümees am Ende des Bandes)
Bachs Kantate "Ich lasse dich nicht, du segnest mich denn" BWV 157. Überlegungen zu Entstehung, Bestimmung und originaler Werkgestalt
Authors: Hofmann Klaus
Published: September 2020

Die Kantate BWV 157 ist nur in Kopien von nach 1750 auf uns gekommen, die eine Abweichung vom Original markieren, dessen Orchestrierung anscheinend verändert und erweitert wird. Das Werk wurde ursprünglich für eine Trauerfeier komponiert, die Anfang 1727 im Dorf Pomßen bei Leipzig unter der Leitung von Bachs Schüler C. G. Wecker stattfand. Eine Kantate, die Bach 1714 in Weimar nach einem Text von G. C. Lehms komponiert haben könnte, diente, leicht überarbeitet, als zweiter Teil der Trauermusik. (Übertragung des englischen Resümees am Ende des Bandes)
Eindeutigkeit und Mehrdeutigkeit in Picanders Kantatenjahrgangs-Vorbemerkung und im Werkverzeichnis des Nekrologs auf Johann Sebastian Bach
Authors: Scheide William H.
Published: September 2020

Dass Christian Friedrich Henrici (alias Picander) auf Bachs Wunsch hin seinen 1728 erschienenen Zyklus von geistlichen Kantatentexten zusammengestellt hat, scheint selbstverständlich zu sein, kann aber faktisch nicht bewiesen werden. Eine kritische Bewertung relevanter Dokumente lässt auch andere Antworten möglich erscheinen. (Übertragung des englischen Resümees am Ende des Bandes)

 

Bezugnehmend auf: Klaus Häfner: Der Picander-Jahrgang. BJ 1975, S. 70-113

William H. Scheide: Bach und der Picander-Jahrgang - Eine Erwiderung. BJ 1980, S. 47-51
Erdmann Neumeister und die Kantatentexte Johann Sebastian Bachs
Authors: Krausse Helmut K.
Published: September 2020

Vergleiche zwischen Neumeisters Kantatentexten und denen anderer Autoren zeigen, wie stark Neumeisters geistliche Dichtung seine Zeitgenossen beeinflusste. Die Texte vieler Kantaten von J. S. Bach enthalten charakteristische Formulierungen, die Nachahmungen des Neumeister-Stils zu versuchen scheinen. (Übertragung des englischen Resümees am Ende des Bandes)
Zur Echtheit und Datierung der Kantate BWV 150 "Nach dir, Herr, verlanget mich"
Authors: Glöckner Andreas
Published: September 2020

Vergleiche auch: Arnold Schering: Die Kantate Nr. 150 "Nach dir, Herr verlanget mich". BJ 1913, S. 39-52

Hans-Joachim Schulze: Rätselhafte Auftragswerke Johann Sebastian Bachs. Anmerkungen zu einigen Kantatentexten. BJ 2010, S. 69-93

Hans-Joachim Schulze: Die Bach-Kantate "Nach dir, Herr verlanget mich" und ihr Meckbach-Akrostichon. BJ 2011, S. 255-257
Bachs Doppelchor "Nun ist das Heil und die Kraft" (BWV 50)
Authors: Hofmann Klaus
Published: September 2020

J.S. Bachs orchesterbegleiteter Doppelchor Nun ist das Heil und die Kraft (BWV 50) ist nur in Abschriften von fremder Hand überliefert. Wichtigste Quelle und Grundlage aller übrigen Abschriften ist die Handschrift SBB P 136 von Carl Gotthelf Gerlach. Das Einzelstück gilt seit Spitta als Teil einer verschollenen Michaeliskantate. Um die Zuverlässigkeit der Überlieferung scheint die Bach-Forschung sich lange Zeit keine Gedanken gemacht zu haben. Der erste, der dies tat, war W[illiam] H. Scheide. (Karin Germerdonk, Quelle: Bibliographie des Musikschrifttums online)

Vergleiche auch: William H. Scheide: "Nun ist das Heil und die Kraft" BWV 50: Doppelchörigkeit, Datierung und Bestimmung. BJ 1982, S. 81-96

Klaus Stein: Stammt "Nun ist das Heil und die Kraft" (BWV 50) von Johann Sebastian Bach? BJ 1999, S. 51-66

Joshua Rifkin: Siegesjubel und Satzfehler. Zum Problem von "Nun ist das Heil und die Kraft" (BWV 50). BJ 2000, S. 67-86

William H. Scheide: Nochmals BWV 50 "Nun ist das Heil und die Kraft". BJ 2001, S. 117-130
Nachbemerkung zu "Neue Bach-Funde" (BJ 1997, S. 7-50)
Authors: Wollny Peter
Published: September 2020

Im Nachtrag zu seinem Artikel im BJ 1997 (Link s.u.) ergänzt der Autor seine dortigen Ausführungen zur Entstehungsgeschichte von BWV 195 um einen Vergleich mit zwei Textvarianten von BWV 34a, die zu dem Schluss führen, der Schlusschor beider Werke sei ein in Bachs ersten Leipziger Jahren regelmäßig von ihm für Trauungen verwendetes Repertoirestück gewesen.

 

Erwähnter Artikel: Peter Wollny: Neue Bach-Funde. BJ 1997, S. 7-50
Stammt "Nun ist das Heil und die Kraft" (BWV 50) von Johann Sebastian Bach?
Authors: Stein Klaus
Published: September 2020

William H. Scheide [RILM 1982-04573-ap] äußerte Zweifel an der Authentizität des Johann Sebastian Bach zugeschriebenen Chores Nun ist das Heil und die Kraft BWV 50. Die Feststellungen, die diese Zweifel veranlassten, werden hier mit Argumenten anderer Autoren und mit Resultaten eigener Arbeiten verglichen. Für derartige Zweifel gibt es keine Veranlassung. Erörtert wird eine Hypothese, die die Besonderheiten in der Struktur dieses Werkes erklärt. (Oliver Schöner, Quelle: Bibliographie des Musikschrifttums online)

Vergleiche auch: William H. Scheide: "Nun ist das Heil und die Kraft" BWV 50: Doppelchörigkeit, Datierung und Bestimmung. BJ 1982, S. 81-96

Klaus Hofmann: Bachs Doppelchor "Nun ist das Heil und die Kraft" (BWV 50). Neue Überlegungen zur Werkgeschichte. BJ 1994, S. 59-73

Joshua Rifkin: Siegesjubel und Satzfehler. Zum Problem von "Nun ist das Heil und die Kraft" (BWV 50). BJ 2000, S. 67-86

William H. Scheide: Nochmals BWV 50 "Nun ist das Heil und die Kraft". BJ 2001, S. 117-130
Johann Christoph Friedrich Bach und die Teilung des väterlichen Erbes
Authors: Wollny Peter
Published: September 2020

Bisher gibt es kaum konkrete Aufschlüsse darüber, im welchem Umfang die beiden jüngsten Söhne Johann Sebastian Bachs, Johann Christoph Friedrich und Johann Christian, aus dem Nachlass des Vaters bedacht wurden. Anhand von Gebrauchsspuren von Originalhandschriften nach 1750 wird die Aufteilung des bachschen Nachlasses diskutiert. Die Ergebnisse werden auf ihre biografische und rezeptionsgeschichtliche Relevanz hin befragt. (Oliver Schöner, Quelle: Bibliographie des Musikschrifttums online)