Growth Through COVID

How COVID impacted my emotional and occupational wellness in a positive manner in order to develop a new outlook on life

RNA Methylation and Ythdf Readers in Posttranscriptional Regulation and Development

Development in animals requires precise and coordinated changes in gene expression. This genetic remodeling is achieved through extensive regulatory networks of proteins and RNAs that function together to specify new cell fates and patterns. One developmental event heavily reliant on these regulatory networks is the maternal-to-zygotic transition (MZT), a universal step in metazoan embryogenesis in which a fertilized oocyte is reprogrammed into a pluripotent embryo. The earliest stages of the MZT are governed by maternally inherited gene products, which are required for cellular functions in the initially transcriptionally silent embryo. To shift developmental control to the zygote, these maternal mRNAs are massively degraded through multiple posttranscriptional mechanisms. The RNA modification, N6-methyladenosine (m6A) has been proposed as a master regulator of mRNA decay during developmental transitions, but the direct effects of this pathway on maternal transcript clearance remain unclear. To determine whether m6A facilitates gene expression changes during the MZT, I employed zebrafish embryos as a model system to dissect the contributions of RNA methylation and its reader proteins to maternal transcript fate. Through transcriptome analysis and reporter assays, I found that m6A controls maternal mRNA degradation by promoting deadenylation. To understand how RNA methylation fits into the framework of known decay pathways, I compared transcripts co-targeted by m6A and miR-430, a microRNA that controls mRNA clearance in zebrafish. This revealed that these mechanisms function independently but additively to promote mRNA degradation, reflecting that methylation modulates transcript abundance in concert with known regulators. To disentangle the roles of the Ythdf proteins that mediate the effects of m6A on mRNA, I generated zebrafish genetic mutants of Ythdf1, Ythdf2, and Ythdf3. Through transcriptomic and phenotypic analysis of these mutants, I determined that global maternal mRNA clearance, zygotic genome activation, and development proceed normally in the absence of any one reader. This revealed that individual Ythdf protein have limited effects on the removal of methylated maternal mRNAs during the MZT. To test if this restricted impact of single Ythdf loss stems from functional redundancy between the readers, I produced double mutants of Ythdf2 and Ythdf3. Double Ythdf deletion prevents female gonad development, indicating that these factors exert overlapping activities during oogenesis. Finally, to fully establish functionally redundancy, I created triple Ythdf mutants, which were larval lethal. I observed this same phenotype in zebrafish lacking the methylases that add m6A to mRNA, indicating that RNA methylation is essential for developmental viability. Together, this work provides insight into the contributions of the m6A modification and its Ythdf effectors to maternal mRNA clearance, and establishes how these key regulators coordinate the gene expression changes that underlie embryonic reprogramming

ANWENDUNG VON IRRFAHRTPROBLEMEN IN DER BESCHREIBUNG DER HYDROLOGISCHEN VORGÄNGE

The connection of the storage and continuation equations, the average delay time and the outflow probability of the water particle are described on the basis of the random walk of water particies. Its comparison to the linear reservoir model. The second part contains lhe different cases of the linear cascade models: dis- crete and continuous, homogenous cascade (Nash) model, superposition oflinear cascades (Dooge model), discrete cascades with feedback, continuous generalized linear cascades, discrete diffuse wave model and its comparison to the cascades having feedback. Finally the time and space discretising conditions coming from the theory of the random walk are demonstrated, which are identical to the criterium of stability of a discretising scherne

Ab Initio Approach to Second-order Resonant Raman Scattering Including Exciton-Phonon Interaction

Raman spectra obtained by the inelastic scattering of light by crystalline solids contain contributions from first-order vibrational processes (e.g. the emission or absorption of one phonon, a quantum of vibration) as well as higher-order processes with at least two phonons being involved. At second order, coupling with the entire phonon spectrum induces a response that may strongly depend on the excitation energy, and reflects complex processes more difficult to interpret. In particular, excitons (i.e. bound electron-hole pairs) may enhance the absorption and emission of light, and couple strongly with phonons in resonance conditions. We design and implement a first-principles methodology to compute second-order Raman scattering, incorporating dielectric responses and phonon eigenstates obtained from density-functional theory and many-body theory. We demonstrate our approach for the case of silicon, relating frequency-dependent relative Raman intensities, that are in excellent agreement with experiment, to different vibrations and regions of the Brillouin zone. We show that exciton-phonon coupling, computed from first principles, indeed strongly affect the spectrum in resonance conditions. The ability to analyze second-order Raman spectra thus provides direct insight into this interaction.Comment: 10 pages, 8 figure

Whole body survey of arterial variants in anatomical donors

Arterial variants, defined as atypical presentations of anatomy including aberrant origin, course, and branching pattern, are important to be aware of because of their effects in the clinical setting as well as their possible link to pathology. Much research has already been done focusing on specific arterial variants in a specific region in the body. However, more research is needed to determine if there is a relationship between arterial variants in different regions of the body. The purpose of this study is to examine the whole-body arterial system of body donors in order to assess if there is a relationship between the presence of arterial variants in one region of the body to the other. The entire arterial system of twenty-five formalin fixed body donors was examined for the presence of arterial variants. The data was separated into two main categories, central variants (e.g. arch of the aorta, unpaired abdominal aortic branches) and peripheral variants (e.g. upper and lower extremities). The relationship between the central and peripheral variants was determined using quantitative observation, specifically, by examining the percent frequency of cases where arterial variants were co-occurring. Of the body donors examined, all were found to have at least one arterial variant, with an average of 8.7 variants per body. Arterial variants were most commonly found in the foregut with prevalence of 80%, the midgut (68%), left subclavian (60%), right upper extremity (52%), and the left upper extremity (48%). Of the central arterial variants, a percent frequency of 20% was found for the arch of the aorta, 20% for the coronary artery, 12% for the hindgut, 28% for the right renal, and 28% for the left renal. For the peripheral variants, the percent frequencies were as follows: brain variants were 4%, right carotid 8%, left carotid 0%, right subclavian 28%, left upper extremity 40%, right suprarenal 24%, left suprarenal 12%, right phrenic 24%, left phrenic 12%, gonadal 4%, right iliac 40%, left iliac 32%, and right lower extremity 40%. Examination of the relationship between central variants and peripheral variants reveals that the most common arterial variants to occur in tandem in the sample were those of the variant foregut with variants of the left subclavian artery (52% of cases), the upper and lower extremities (36-44% and 40-44% of cases, respectively), and the right iliac artery (36% of cases). The most common central arterial variants to co-occur were the variants of the foregut and midgut observed in 64% of cases. The frequency of cases involving normal central anatomy and variant peripheral anatomy indicates that vascular variants in the periphery are likely unrelated to variants in the central body cavities. However, it does seem like there are “hot spots” for arterial variants to occur, including the foregut, midgut left subclavian artery, right and left upper extremities, the right iliac artery, and the right and left lower extremities. Although there was no discernable pattern found between vascular variants in the present study, that does not preclude the possibility that there is a significant relationship between certain vascular variants. Either way, the high prevalence of cases with multiple arterial variations suggests that they may be more likely to occur than previously thought