DNA serves as nature's information storage molecule, and has been the primary focus of engineered systems for biological computing and data storage. Here we combine recent efforts in DNA self-assembly and toehold-mediated strand displacement to develop a rewritable multi-bit DNA memory system. The system operates by encoding information in distinct and reversible conformations of a DNA nanoswitch and decoding by gel electrophoresis. We demonstrate a 5-bit system capable of writing, erasing, and rewriting binary representations of alphanumeric symbols, as well as compatibility with ‘OR’ and ‘AND’ logic operations. Our strategy is simple to implement, requiring only a single mixing step at room temperature for each operation and standard gel electrophoresis to read the data. We envision such systems could find use in covert product labeling and barcoding, as well as secure messaging and authentication when combined with previously developed encryption strategies. Ultimately, this type of memory has exciting potential in biomedical sciences as data storage can be coupled to sensing of biological molecules.

SUMMARY Maternal mRNAs synthesized during oogenesis initiate the development of future generations. Some maternal mRNAs are either somatic or germline determinants and must be translationally repressed until embryogenesis. However, the translational repressors themselves are temporally regulated. We used polar granule component (pgc), a Drosophila maternal mRNA, to ask how maternal transcripts are repressed while the regulatory landscape is shifting. pgc, a germline determinant, is translationally regulated throughout oogenesis. We find that different conserved RNA-binding proteins bind a 10-nt sequence in the 3′ UTR of pgc mRNA to continuously repress translation at different stages of oogenesis. Pumilio binds to this sequence in undifferentiated and early-differentiating oocytes to block Pgc translation. After differentiation, Bruno levels increase, allowing Bruno to bind the same sequence and take over translational repression of pgc mRNA. We have identified a class of maternal mRNAs that are regulated similarly, including zelda, the activator of the zygotic genome.

The centrifuge force microscope (CFM) was recently introduced as a platform for massively parallel single-molecule manipulation and analysis. Here we developed a low-cost and self-contained CFM module that works directly within a commercial centrifuge, greatly improving accessibility and ease of use. Our instrument incorporates research grade video microscopy, a power source, a computer, and wireless transmission capability to simultaneously monitor many individually tethered microspheres. We validated the instrument by performing single-molecule force shearing of short DNA duplexes. For a 7 bp duplex, we observed over 1000 dissociation events due to force dependent shearing from 2 pN to 12 pN with dissociation times in the range of 10-100 s. We extended the measurement to a 10 bp duplex, applying a 12 pN force clamp and directly observing single-molecule dissociation over an 85 min experiment. Our new CFM module facilitates simple and inexpensive experiments that dramatically improve access to single-molecule analysis.

Abstract:The centrifuge force microscope (CFM) was recently introduced as a platform for massively parallel single-molecule manipulation and analysis. Here we developed a low-cost and selfcontained CFM module that works directly within a commercial centrifuge, greatly improving accessibility and ease of use. Our instrument incorporates research grade video microscopy, a power source, a computer, and wireless transmission capability to simultaneously monitor many individually tethered microspheres. We validated the instrument by performing single-molecule force shearing of short DNA duplexes. For a 7 bp duplex, we collected over 1000 statistics of force dependent shearing kinetics from 2 pN to 12 pN with dissociation times in the range of 10-100 seconds. We extended the measurement to a 10 bp duplex, applying a 12 pN force clamp and directly observing single-molecule dissociation over an 85 minute experiment. Our new CFM module facilitates simple and inexpensive experiments that dramatically improve access to singlemolecule analysis.

32Maternal mRNAs are synthesized during oogenesis to initiate the development of future 33 generations. Some maternal mRNAs are determinants of somatic or germline fate and 34 must be translationally repressed until embryogenesis. However, the translational 35 repressors themselves are also temporally regulated. We use polar granule component 36 (pgc), a Drosophila maternal mRNA, as a model system to ask how maternal mRNAs 37 are repressed while the regulatory landscape is continually shifting. pgc, a potent 38 transcriptional silencer and germline determinant, is translationally regulated throughout 39 oogenesis. We find that the 3'UTR of pgc mRNA contains a conserved ten-nucleotide 40 sequence that is bound by different conserved RNA binding proteins (RBPs) at different 41 stages of oogenesis to continuously repress translation except for a brief expression in 42 the stem cell daughter. Pumilio (Pum) binds to this sequence in undifferentiated and 43 early differentiating oocytes and recruits other temporally restricted translational 44 regulators to block pgc translation. After differentiation, Pum levels diminish and Bruno 45 (Bru) levels increase, allowing Bru to bind the same 3'UTR sequence and take over 46 translational repression of pgc mRNA. We have identified a class of maternal mRNAs 47 regulated during oogenesis by both Pum and Bru, including Zelda, activator of the 48 zygotic genome, which contain this core 10-nt regulatory sequence. Our data suggests 49 that this hand off mechanism is more generally utilized to inhibit translation of maternal 50 mRNAs during oogenesis.

Context: Major Depressive Disorder (MDD) is the most prevalent psychiatric illness and escitalopram is one of the most commonly used selective serotonin reuptake inhibitors (SSRI) for its treatment. Aim: To study efficacy and safety of escitalopram in patients with first episode of MDD. Materials and methods: This was a prospective, open label, eight weeks follow-up study. Eighty-four patients with first episode of MDD were selected using simple random sampling. Depression was diagnosed using DSM-5 diagnostic criteria for MDD. Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess the severity of depression. Clinical Global Impression Severity (CGI-S) and Clinical Global Impression Improvement (CGI-I) were used to measure illness severity and global improvement. The Antidepressant Side-Effect Checklist (ASEC) was used to measure adverse reactions to antidepressants. Results: The mean of MADRS total score at baseline was 32.08 which was decrease in subsequent follow up and at 8-week score was 11.24. 77% of patients responded (≥50% or more reduction of MADRS total score) and 64.9% remitted (≤12 score of MADRS) at 8 weeks. 22.9% of patients reported side effects during the 8-week treatment. 94.2% of patients got significant improvement with 10 mg dose of escitalopram. The common side effects were constipation (5.4%), nausea (5.4%), dry mouth (4.1%) and yawning (4.15%). Conclusion: Escitalopram treatment was efficacious and well tolerated in patients with first episode of MDD. Nearly two third patients achieved remission at the end of eight week.

Throughout the beyond a decade, Food Rule Experts have deduced that caffeine usage isn't risky at whatever point consumed at levels of 200 mg at a time (around 2½ cups of coffee) or 400 mg everyday (around 5 cups of coffee). Moreover, caffeine has various positive exercises on the frontal cortex. It can augment availability and success, help obsession, further foster perspective likewise, limit distress. Caffeine could disturb rest, regardless, simply in fragile individuals. It could raise anxiety in a little subset of particularly fragile people. Caffeine does not seem to provoke dependence, yet a minority of people experience withdrawal secondary effects. Caffeine can potentiate the effect of standard torment alleviating drugs in cerebral agony and migraine. Well established coffee/caffeine usage has been connected with expectation of mental disintegration, and diminished risk of making stroke, Parkinson's ailment and Alzheimer's ailment. Its usage does not seem to influence seizure occasion. Thusly, everyday coffee and caffeine confirmation can be significant for a strong changed diet; its use does not ought to be ended in elderly people.