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[
Biochemistry,
2020]
Asymmetric cell division (ACD) is a conserved strategy for achieving cell diversity. A cell can undergo an intrinsic ACD through asymmetric segregation of cell fate determinants or cellular organelles. Recently, a new biophysical concept known as biomolecular phase separation, through which proteins and/or RNAs autonomously form a highly concentrated non-membrane-enclosed compartment via multivalent interactions, has provided new insights into the assembly and regulation of many membrane-less or membrane-attached organelles. Intriguingly, biomolecular phase separation is suggested to drive asymmetric condensation of cell fate determinants during ACD as well as organization of cellular organelles involved in ACD. In this Perspective, I first summarize recent findings on the molecular basis governing intrinsic ACD. Then I will discuss how ACD might be regulated by formation of dense molecular assemblies via phase separation.
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Opt Express,
2010]
Over the last decade microfluidics has created a versatile platform that has significantly advanced the ways in which micro-scale organisms and objects are controlled, processed and investigated, by improving the cost, compactness and throughput aspects of analysis. Microfluidics has also expanded into optics to create reconfigurable and flexible optical devices such as reconfigurable lenses, lasers, waveguides, switches, and on-chip microscopes. Here we present a new opto-fluidic microscopy modality, i.e., Holographic Opto-fluidic Microscopy (HOM), based on lensless holographic imaging. This imaging modality complements the miniaturization provided by microfluidics and would allow the integration of microscopy into existing on-chip microfluidic devices with various functionalities. Our imaging modality utilizes partially coherent in-line holography and pixel super-resolution to create high-resolution amplitude and phase images of the objects flowing within micro-fluidic channels, which we demonstrate by imaging C. elegans, Giardia lamblia, and Mulberry pollen. HOM does not involve complicated fabrication processes or precise alignment, nor does it require a highly uniform flow of objects within microfluidic channels.
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Neuron,
2021]
Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on the efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function. Traditionally, these two approaches were developed independently and applied separately. Here, we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy "optimization priors." This family defines a smooth interpolation between a data-rich inference regime and a data-limited prediction regime. Using three neuroscience datasets, we demonstrate that our framework allows one to address fundamental challenges relating to inference in high-dimensional, biological problems.
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BMC Bioinformatics,
2019]
BACKGROUND: Third-generation sequencing platforms, such as PacBio sequencing, have been developed rapidly in recent years. PacBio sequencing generates much longer reads than the second-generation sequencing (or the next generation sequencing, NGS) technologies and it has unique sequencing error patterns. An effective read simulator is essential to evaluate and promote the development of new bioinformatics tools for PacBio sequencing data analysis. RESULTS: We developed a new PacBio Sequencing Simulator (PaSS). It can learn sequence patterns from PacBio sequencing data currently available. In addition to the distribution of read lengths and error rates, we included a context-specific sequencing error model. Compared to existing PacBio sequencing simulators such as PBSIM, LongISLND and NPBSS, PaSS performed better in many aspects. Assembly tests also suggest that reads simulated by PaSS are the most similar to experimental sequencing data. CONCLUSION: PaSS is an effective sequence simulator for PacBio sequencing. It will facilitate the evaluation and development of new analysis tools for the third-generation sequencing data.
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Worm,
2013]
The activity and assembly of various myosin subtypes is coordinated by conserved UCS (UNC-45/CRO1/She4p) domain proteins. One founding member of the UCS family is the Caenorhabditis elegans UNC-45 protein important for the organization of striated muscle filaments. Our recent structural and biochemical results demonstrated that UNC-45 forms a protein chain with defined periodicity of myosin interaction domains. Intriguingly, the UNC-45 chain serves as docking platform for myosin molecules, which promotes ordered spacing and incorporation of myosin into contractile muscle sarcomeres. The physiological relevance of this observation was demonstrated in C. elegans by transgenic expression of UNC-45 chain formation mutants, which provokes defects in muscle structure and size. Collaborating with the molecular chaperones, Hsp70 and Hsp90, chain formation of UNC-45 links myosin folding with myofilament assembly. Here, we discuss our recent findings on the dynamic regulation of UNC-45 structure and stability in the context of muscle regeneration mechanisms that are affected in myopathic diseases and during aging.
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CNS Drugs,
2013]
Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.
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Cutis,
2000]
Onchocerciasis, or river blindness, is a parasitic infection caused by the filarial nematode, Onchocerca volvulus. It infects 18 million people worldwide, but is rarely seen in the United States. It is one of the leading causes of blindness in the developing world. Although onchocerciasis is also known as river blindness, it is not just a disease of the eyes, but rather a chronic multisystem disease. Clinically, onchocerciasis takes three forms: 1) eye disease; 2) subcutaneous nodules; and 3) a pruritic hypopigmented or hyperpigmented papular dermatitis. We present an 18-year-old African female with a 5-year history of asymptomatic, hypopigmented, slightly atrophic macules on her anterior tibiae. Pathology revealed a scant perivascular inflammatory infiltrate with mononuclear cells, eosinophils, and rare microfilariae in the papillary dermis. Ivermectin is the treatment of choice for onchocerciasis and was initiated in this patient. We present this interesting patient with onchocerciasis to expand our differential of hypopigmented macules, especially in the African population. In addition, we discuss both the diagnosis and the treatment of onchocerciasis in expatriate patients living in nonendemic areas.
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RNA Biol,
2016]
microRNAs (miRNAs) are an abundant class of small endogenous non-coding RNAs (ncRNAs) of 22 nucleotides (nts) in length. These small regulatory molecules are involved in diverse developmental, physiological and pathological processes. miRNAs target mRNAs (mRNAs) for translational repression and/or mRNA degradation. Predictions of miRNA binding sites facilitate experimental validation of miRNA targets. Models developed with data from CLIP studies have been used for predictions of miRNA binding sites in the whole transcriptomes of human, mouse and worm. The prediction results have been assembled into STarMirDB, a new database of miRNA binding sites available at
http://sfold.wadsworth.org/starmirDB.php . STarMirDB can be searched by miRNAs or mRNAs separately or in combination. The search results are categorized into seed and seedless sites in 3' UTR, CDS and 5' UTR. For each predicted site, STarMirDB provides a comprehensive list of sequence, thermodynamic and target structural features that are known to influence miRNA: target interaction. A high resolution PDF diagram of the conformation of the miRNA:target hybrid is also available for visualization and publication. The results of a database search are available through both an interactive viewer and downloadable text files.
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Autophagy,
2012]
Autophagy is a catabolic process through which damaged organelles and protein aggregates are delivered to lysosomes for degradation. Autophagy genes are reported to promote exposure of "eat me" signals on the surface of apoptotic cells, but whether they function in engulfing cells is not clear. Recently, we found that the autophagy mutants
atg-18 and
epg-5 are defective in removing apoptotic cells derived from the C. elegans Q neuroblast, a phenotype that can be fully rescued by expression of ATG-18 and EPG-5 in the engulfing cell. Loss of ATG-18 or EPG-5 does not affect cell corpse engulfment but causes defects in phagosomal recruitment of RAB-5 and RAB-7 and formation of phagolysosomes. EPG-5, ATG-18 and LGG-1 are sequentially recruited to phagosomes, suggesting that they function at different steps of phagosomal maturation. Our studies indicate that autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell.
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Oecologia,
1997]
The effects of natural nematode communities on bacterial activity and abundance were investigated in a microcosm study. Nematodes were added at different densities to a freshwater sediment and bacterial parameters were measured after 1, 5, 9, and 17 days. Significant effects of nematode density on bacterial activity were noted on day 5. No long-term changes in bacterial activity were recorded. Bacterial abundance displayed an overall decrease in both treatments and controls. In a second experiment, the effect of nematode feeding-type on bacterial activity was studied. Microcosms were incubated with 100 individuals of a fungus-feeding (Aphelenchus avenae) or a bacteria-feeding nematode species (Caenorhabditis elegans) respectively, and bacterial activity was determined after 0, 1, 2, 4, and 7 days. Significant time and feeding-type effects were found, with consistently higher bacterial activity estimates in treatments with bacteria-feeding nematodes. These results suggest that grazing affects bacterial activity, and indicate that grazing by nematodes may be more important in stimulating bacterial activity than bioturbation or excretion. Combining these results, we conclude that natural nematode communities may have an impact on bacterial activity, and that the magnitude of this impact depends on the proportion of actively feeding bactivores within the community.