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https://www.readbyqxmd.com/read/29058193/combinatorial-assembly-of-lumitoxins
#1
David Nedrud, Daniel Schmidt
Ion channels are among the most important proteins in neuroscience and serve as drug targets for many brain disorders. During development, learning, disease progression, and other processes, the activity levels of specific ion channels are tuned in a cell-type specific manner. However, it is difficult to assess how cell-specific changes in ion channel activity alter emergent brain functions. We have developed a protein architecture for fully genetically encoded light-activated modulation of endogenous ion channel activity...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29058102/procaspase-activating-compound-1-induces-apoptosis-in-trypanosoma-cruzi
#2
Emanuella de Castro, Thamile Luciane Reus, Alessandra Melo de Aguiar, Andrea Rodrigues Ávila, Tatiana de Arruda Campos Brasil de Souza
Some therapeutics for parasitic, cardiac and neurological diseases activate apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is relevant. However, the molecular mechanism of apoptosis in unicellular organisms remain elusive, despite morphological evidence of its occurrence. In Trypanosoma cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to have a key role in parasite apoptosis. Accordingly, this work provides data concerning TcMCA3 regulation through its interaction with procaspase-activating compound 1 (PAC-1), a procaspase 3 activator...
October 20, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29056362/critical-appraisal-of-pathology-transmission-in-the-%C3%AE-synuclein-fibril-model-of-lewy-body-disorders
#3
Negin Nouraei, Daniel M Mason, Kristin M Miner, Michael A Carcella, Tarun N Bhatia, Benjamin K Dumm, Dishaben Soni, David A Johnson, Kelvin C Luk, Rehana K Leak
Lewy body disorders are characterized by the emergence of α-synucleinopathy in many parts of the central and peripheral nervous systems, including in the telencephalon. Dense α-synuclein(+) pathology appears in regio inferior of the hippocampus in both Parkinson's disease and dementia with Lewy bodies and may disturb cognitive function. The preformed α-synuclein fibril model of Parkinson's disease is growing in use, given its potential for seeding the self-propagating spread of α-synucleinopathy throughout the mammalian brain...
October 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29055695/conserved-expression-of-ultra-conserved-noncoding-rna-in-mammalian-nervous-system
#4
Junjie Zhou, Ruiyu Wang, Jing Zhang, Liyuan Zhu, Wei Liu, Shuaiyao Lu, Pan Chen, Hanlu Li, Bin Yin, Jiangang Yuan, Boqin Qiang, Pengcheng Shu, Xiaozhong Peng
T-UCRs, a class of long non-coding RNAs that are transcribed from ultra-conserved regions (UCRs), might play an important role in development and diseases. However, the amount of T-UCRs that are conservatively expressed in the developing nervous systems of mice, monkeys and humans is still unknown. In this study, we screened the RNA sequence signals of 481 identified UCRs in an E14.5 mouse brain from the ENCODE database and found 76 UCRs that may be transcribed into T-UCRs. To verify the expression of these potential T-UCRs, we used an RT-PCR experiment and identified that 60 T-UCRs can be expressed in the E14...
October 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29054266/circulating-peptidome-and-tumor-resident-proteolysis
#5
Jia Fan, Bo Ning, Christopher J Lyon, Tony Y Hu
Mammalian proteases segregate into several distinct protein families that employ different functional domains to hydrolyze peptides bonds with different specificities and affinities. These enzymes play central roles in critical cellular and systemic processes, including regulation of cell growth, differentiation, homeostasis, and apoptosis; and cancer initiation, progression, and metastasis. Human proteases segregate into five distinct catalytic classes; the metalloprotease, serine protease, and cysteine protease families have the most members, while the aspartic and threonine peptidase families have relatively few examples...
2017: Enzymes
https://www.readbyqxmd.com/read/29053845/substitution-of-yor1p-nbd1-residues-improves-the-thermal-stability-of-human-cystic-fibrosis-transmembrane-conductance-regulator
#6
B M Xavier, E Hildebrandt, F Jiang, H Ding, J C Kappes, I L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a plasma membrane chloride channel protein that regulates vertebrate fluid homeostasis. The inefficiency of wild type human CFTR protein folding/trafficking is exacerbated by genetic mutations that can cause protein misfolding in the endoplasmic reticulum (ER) and subsequent degradation. This project investigates small changes in protein sequence that can alter the thermal stability of the large multi-domain CFTR protein. We target a conserved 70-residue α-subdomain located in the first nucleotide-binding domain that hosts the common misfolding mutation ∆F508...
October 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29053696/3-end-sequencing-library-preparation-with-a-seq2
#7
Georges Martin, Ralf Schmidt, Andreas J Gruber, Souvik Ghosh, Walter Keller, Mihaela Zavolan
Studies in the last decade have revealed a complex and dynamic variety of pre-mRNA cleavage and polyadenylation reactions. mRNAs with long 3' untranslated regions (UTRs) are generated in differentiated cells whereas proliferating cells preferentially express transcripts with short 3'UTRs. We describe the A-seq protocol, now at its second version, which was developed to map polyadenylation sites genome-wide and study the regulation of pre-mRNA 3' end processing. Also this current protocol takes advantage of the polyadenylate (poly(A)) tails that are added during the biogenesis of most mammalian mRNAs to enrich for fully processed mRNAs...
October 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053599/gut-fermentation-of-dietary-fibres-physico-chemistry-of-plant-cell-walls-and-implications-for-health
#8
REVIEW
Barbara A Williams, Lucas J Grant, Michael J Gidley, Deirdre Mikkelsen
The majority of dietary fibre (DF) originates from plant cell walls. Chemically, DF mostly comprise carbohydrate polymers, which resist hydrolysis by digestive enzymes in the mammalian small intestine, but can be fermented by large intestinal bacteria. One of the main benefits of DF relate to its fermentability, which affects microbial diversity and function within the gastro-intestinal tract (GIT), as well as the by-products of the fermentation process. Much work examining DF tends to focus on various purified ingredients, which have been extracted from plants...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#9
Helen Court, Ian M Ahearn, Marc Amoyel, Erika A Bach, Mark R Philips
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-Kras(G12D) mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency...
October 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29051181/disorders-of-erythrocyte-hydration
#10
Patrick G Gallagher
The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29050336/transcriptional-downregulation-of-microrna-19a-by-ros-production-and-nf-%C3%AE%C2%BAb-deactivation-governs-resistance-to-oxidative-stress-initiated-apoptosis
#11
Jun Hong, Ying Wang, Bang-Chuan Hu, Liang Xu, Jing-Quan Liu, Min-Hua Chen, Jin-Zhu Wang, Fang Han, Yang Zheng, Xu Chen, Qian Li, Xiang-Hong Yang, Ren-Hua Sun, Shi-Jing Mo
Cell apoptosis is one of the main pathological alterations during oxidative stress (OS) injury. Previously, we corroborated that nuclear factor-κB (NF-κB) transactivation confers apoptosis resistance against OS in mammalian cells, yet the underlying mechanisms remain enigmatic. Here we report that microRNA-19a (miR-19a) transcriptionally regulated by reactive oxygen species (ROS) production and NF-κB deactivation prevents OS-initiated cell apoptosis through cylindromatosis (CYLD) repression. CYLD contributes to OS-initiated cell apoptosis, for which NF-κB deactivation is essential...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048631/autophagy-induction-enhances-tetrandrine-induced-apoptosis-via-the-ampk-mtor-pathway-in-human-bladder-cancer-cells
#12
Bo Kou, Wei Liu, Xu Xu, Yang Yang, Qiuyue Yi, Fengwei Guo, Jianpeng Li, Jinsong Zhou, Qingshan Kou
Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29047191/wnt-signalling-pathways-in-skin-development-and-epidermal-stem-cells
#13
REVIEW
Anthony Veltri, Christopher Lang, Wen-Hui Lien
Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF...
October 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/29046633/activity-dependent-phosphorylation-by-camkii%C3%AE-alters-the-ca-2-affinity-of-the-multi-c2-domain-protein-otoferlin
#14
Sandra Meese, Andreia P Cepeda, Felix Gahlen, Christopher M Adams, Ralf Ficner, Anthony J Ricci, Stefan Heller, Ellen Reisinger, Meike Herget
Otoferlin is essential for fast Ca(2+)-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca(2+)/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ) as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29046447/a-functional-carboxy-terminal-fluorescent-protein-fusion-to-pseudorabies-virus-small-capsid-protein-vp26
#15
Ian B Hogue, Jolie Jean, Andrew D Esteves, Nikhila S Tanneti, Julian Scherer, Lynn W Enquist
Fluorescent protein fusions to herpesvirus capsids have proven to be a valuable method to study virus particle transport in living cells. Fluorescent protein fusions to the amino terminus of small capsid protein VP26 are the most widely-used method to visualize Pseudorabies Virus (PRV) and Herpes Simplex Virus (HSV) particles in living cells. However, these fusion proteins do not incorporate to full occupancy, and have modest effects on virus replication and pathogenesis. Recent cryo electron microscopy studies have revealed that herpesvirus small capsid proteins bind to capsids via their amino terminus, whereas the carboxy terminus is unstructured and may therefore better tolerate fluorescent protein fusions...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046352/the-lignan-manassantin-is-a-potent-and-specific-inhibitor-of-mitochondrial-complex-i-and-bioenergetic-activity-in-mammals
#16
Yibao Ma, Hae-Ki Min, Unsong Oh, Adam M Hawkridge, Wei Wang, Ahmed A Mohsin, Qun Chen, Arun Sanyal, Edward J Lesnefsky, Xianjun Fang
Dineolignans manassantin A and B from the plant Saururus cernuus are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-kappaB, MAPK, STAT3 and hypoxia-inducible factor 1 alpha (HIF-1alpha). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin in vivo. Moreover, it has been recently reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29046344/kinetochore-microtubule-interactions-in-chromosome-segregation-lessons-from-yeast-and-mammalian-cells
#17
REVIEW
Geethu Emily Thomas, Marira R Renjith, Tapas K Manna
Chromosome congression and segregation require robust yet dynamic attachment of the kinetochore with the spindle microtubules. Force generated at the kinetochore-microtubule interface plays a vital role to drive the attachment, as it is required to move chromosomes and to provide signal to sense correct attachments. To understand the mechanisms underlying these processes, it is critical to describe how the force is generated and how the molecules at the kinetochore-microtubule interface are organized and assembled to withstand the force and respond to it...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29045898/peptidoglycan-sensing-receptors-trigger-the-formation-of-functional-amyloids-of-the-adaptor-protein-imd-to-initiate-drosophila-nf-%C3%AE%C2%BAb-signaling
#18
Anni Kleino, Nancy F Ramia, Gunes Bozkurt, Yanfang Shen, Himani Nailwal, Jing Huang, Johanna Napetschnig, Monique Gangloff, Francis Ka-Ming Chan, Hao Wu, Jixi Li, Neal Silverman
In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each contain a motif with some resemblance to the RIP Homotypic Interaction Motif (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids during necroptosis. Here we found that despite sequence divergence, these Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045879/probing-cell-adhesion-profiles-with-a-microscale-adhesive-choice-assay
#19
Harsha Kittur, Andy Tay, Avery Hua, Min Yu, Dino Di Carlo
In this work, we introduce, to our knowledge, a new set of adhesion-based biomarkers for characterizing mammalian cells. Mammalian cell adhesion to the extracellular matrix influences numerous physiological processes. Current in vitro methods to probe adhesion focus on adhesive force to a single surface, which can investigate only a subcomponent of the adhesive, motility, and polarization cues responsible for adhesion in the 3D tissue environment. Here, we demonstrate a method to quantify the transhesive properties of cells that relies on the microscale juxtaposition of two extracellular matrix-coated surfaces...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045493/the-sequence-preference-of-dna-methylation-variation-in-mammalians
#20
Ling Zhang, Chan Gu, Lijiang Yang, Fuchou Tang, Yi Qin Gao
Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The CpG methylation level shows a bimodal distribution but the bimodality can be overestimated due to the heterogeneity of per-base depth. Here, we developed an algorithm to eliminate the effect of per-base depth inhomogeneity on the bimodality and obtained a random CpG methylation distribution. By quantifying the deviation of the observed methylation distribution and the random one using the information formula, we find that in tetranucleotides 5'-N5CGN3-3' (N5, N3 = A, C, G or T), GCGN3 and CCGN3 show less apparent deviation than ACGN3 and TCGN3, indicating that GCGN3 and CCGN3 are less variant in their level of methylation...
2017: PloS One
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