An Investigation Into The Molecular Basis Underlying Enhancement Of Transcription By The Intron In Budding Yeast

It is now quite evident that the introns, which are removed from the primary transcript by the process of splicing, are involved in a variety of important functions in eukaryotic cells. One of the evolutionarily conserved functions of introns is their role in regulating transcription of genes that harbors them. This effect of a splicing-competent intron on transcription is known as ‘Intron-Mediated Enhancement of transcription’ (IME). It has been observed that the intron-containing genes are often transcribed more efficiently than non-intronic genes. However, the molecular mechanism underlying IME in budding yeast and higher eukaryotes is not entirely clear, and that forms the basis of my thesis. To address this issue, I have organized my research project into three specific aims. The primary objective of the first aim was to investigate the mechanism of enhancement of transcription by an intron. I found that the intron-mediated enhancement in budding yeast is dependent on the gene assuming a unique architecture called gene loop. In the second aim, I explored the molecular basis underlying enhancement of transcription by the intron-facilitated gene loop. In the third aim, I determined the effect of position of an intron within a gene on its transcription regulatory potential. In the first aim, I randomly selected six genes and compared their transcription in the presence and absence of an intron by strand-specific TRO approach. I observed a sharp decline in transcription in the absence of intron. Furthermore, I found that the gene assumed a looped conformation in the presence of an intron. Intron-dependent gene loop was stabilized by three types of interactions; the promoter-terminator, the promoter-5’ splice site and the terminator-3ꞌ splice site interactions. More importantly, I found that the intron-dependent enhancement was completely dependent on gene looping as no enhancement of transcription by an intron was observed in the looping defective mutant. In the second aim, I investigated how the intron-mediated gene looping regulates transcription. My hypothesis was that intron-mediated gene looping confers directionality, and thereby enhances transcription. During initiation of transcription, the promoter-bound RNAP II has a tendency to transcribe both the downstream coding region in sense direction producing mRNA, as well as the upstream non-coding region in the anti-sense direction producing uaRNA (upstream-antisense RNA). However, there are certain checkpoints in the cell that allows the selective transcription in the sense direction over anti-sense direction, hence maintaining promoter directionality. My results reveal that the intron-dependent gene looping facilitates the recruitment of termination factors in the promoter-proximal region. These termination factors then selectively terminates the uaRNA synthesis, and hence confers directionality. My last aim was to see the effect of position of an intron within a gene on transcription of the gene. The generally accepted view is that the intron should be present close to the 5ꞌ end of the gene to bring about enhancement of transcription. Whether the presence of intron near the 3ꞌ end of the gene results in enhancement of transcription in yeast was unclear. To address the issue, I inserted the intron in the intron-less version of IMD4 gene at three positions, and showed that even the terminator-proximal intron can enhance transcription. Till now my results have shown that the terminal-proximal intron also enhances transcription in a way similar to the promoter-proximal intron, that is, by conferring promoter directionality

Pancytopenia in pregnant patients with COVID-19 infection and vitamin B12 deficiency: a case report study

Background: Folate and vitamin B 12 deficiency can lead to pancytopenia in pregnancy. Some cases of pancytopenia due to COVID-19 infection have also been reported. The two cases that we present are related to the coincidence of pregnancy and deficiency of folic acid and vitamin B12 with COVID-19 infection. Case presentation: A 26-year- woman G3P1L1A1 and 21-year-woman G2P1L1 presented with pancytopenia and mild COVID-19 infection. The antenatal period was uneventful, and both cases also had folate and vitamin B12 deficiency. They received blood products, folic acid, and vitamin B12 supplementation. COVID- 19 infection was managed well with analgesic and vital monitoring. Postpartum hemorrhage occurred in the second case, which was well managed with uterotonics. All laboratory parameters came out to be normal after three months of supplementation of folic acid and vitamin B12. Conclusion: Pancytopenia in pregnancy due to folate and vitamin B12 deficiency and COVID- 19 infection can be easily managed with timely intensive targeted therapy, but we should be extra vigilant while handling such complicated cases, keeping in mind all possible differential diagnoses for pancytopenia

A Survey on Energy Efficient Routing In MANETs Using Multi-Objective Genetic Algorithm

Mobile ad hoc networks (MANET) are self-establishing network that contains short radio range and limited bandwidth and they do not have any specified infrastructure. The ad hoc network changes its topology suddenly. In such this type of situation, establishing correct and efficient routes from source to destination is an important design issue in mobile ad hoc networks and its challenging goal is to provide energy efficient routing protocol. For finding the shortest path between the sources to destination, the routing technique genetic algorithm (GA) plays an important role. Such type of routing technique will reduce in finding the route again and again when any failure occurs in the path. Hence, it will take less time in sending again the packet to the destination and therefore it results in increasing throughput in the Mobile Ad hoc Network. In this paper, we have discussed the routing protocols, its classifications, advantage and disadvantages of the routing protocols and taxonomy of energy efficient routing protocols in Mobile Ad hoc network. DOI: 10.17762/ijritcc2321-8169.160411

Appropriate Utilization of Diabetic Diets for Inpatients

AIM: To increase the number of diabetic patients that are ordered a diabetic diet at time of admission So that blood sugars may be better controlled throughout admission with decreased usage of CDIhttps://jdc.jefferson.edu/patientsafetyposters/1017/thumbnail.jp

Nodding Syndrome - an Indian case

Background: Although nodding syndrome is a catastrophic epileptic encephalopathy, it is reported only from Africa so far. We describe the first case from the Indian sub-continent.Methods: A ten-year-old child who had an episode of Guillain Barre syndrome with incomplete recovery developed emaciation secondary to bulbar palsy and depression. Subsequently, nine months later she developed head nodding, spastic quadriparesis, choreo-athetoid movement disorder, global aphasia and depression. She improved with sodium valproate, nutritional rehabilitation and anti-spasticity and anti-depressant medications.Results: First case of nodding syndrome is described from India where possible etiology is malnutrition. She had anemia, her electroencephalography revealed parieto-occipital inter-ictal epileptiform discharges and Magnetic Resonance Imaging showed diffuse cerebral atrophy.Conclusion: Nodding syndrome is an epileptic encephalopathy of nutritional origin beyond geographical barriers but amenable to anti-convulsants and nutritional rehabilitation.Keywords: Nodding syndrome, India

Paving the Path for Heterogeneous Memory Adoption in Production Systems

Systems from smartphones to data-centers to supercomputers are increasingly heterogeneous, comprising various memory technologies and core types. Heterogeneous memory systems provide an opportunity to suitably match varying memory access pat- terns in applications, reducing CPU time thus increasing performance per dollar resulting in aggregate savings of millions of dollars in large-scale systems. However, with increased provisioning of main memory capacity per machine and differences in memory characteristics (for example, bandwidth, latency, cost, and density), memory management in such heterogeneous memory systems poses multi-fold challenges on system programmability and design. In this thesis, we tackle memory management of two heterogeneous memory systems: (a) CPU-GPU systems with a unified virtual address space, and (b) Cloud computing platforms that can deploy cheaper but slower memory technologies alongside DRAMs to reduce cost of memory in data-centers. First, we show that operating systems do not have sufficient information to optimally manage pages in bandwidth-asymmetric systems and thus fail to maximize bandwidth to massively-threaded GPU applications sacrificing GPU throughput. We present BW-AWARE placement/migration policies to support OS to make optimal data management decisions. Second, we present a CPU-GPU cache coherence design where CPU and GPU need not implement same cache coherence protocol but provide cache-coherent memory interface to the programmer. Our proposal is first practical approach to provide a unified, coherent CPU–GPU address space without requiring hardware cache coherence, with a potential to enable an explosion in algorithms that leverage tightly coupled CPU–GPU coordination. Finally, to reduce the cost of memory in cloud platforms where the trend has been to map datasets in memory, we make a case for a two-tiered memory system where cheaper (per bit) memories, such as Intel/Microns 3D XPoint, will be deployed alongside DRAM. We present Thermostat, an application-transparent huge-page-aware software mechanism to place pages in a dual-technology hybrid memory system while achieving both the cost advantages of two-tiered memory and performance advantages of transparent huge pages. With Thermostat’s capability to control the application slowdown on a per application basis, cloud providers can realize cost savings from upcoming cheaper memory technologies by shifting infrequently accessed cold data to slow memory, while satisfying throughput demand of the customers.PHDComputer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137052/1/nehaag_1.pd

Comparative evaluation of the efficacy and safety of ormeloxifene and norethisterone in dysfunctional uterine bleeding

Background: Dysfunctional Uterine Bleeding (DUB) is the most common cause of abnormal uterine bleeding and is a major indication for referral to gynecological clinics. There are very few studies comparing the effect of ormeloxifene and progesterone in DUB. The objective of the study was to assess the efficacy and safety of Ormeloxifene in DUB and compare it with Norethisterone.Methods: Hundred women presenting with DUB were randomly allocated to 2 equal groups, Group-A, which received 60mg ormeloxifene twice a week for 12 weeks followed by 60mg once a week for next 12 weeks and Group-B, which received 5mg norethisterone twice daily for 21 days for 6 cycles. The primary outcomes were reduction in menstrual blood loss [measured by fall in PBAC (Pictorial Blood loss Assessment Chart) score and subjective assessment], rise in hemoglobin level and decrease in endometrial thickness.Results: The reduction in mean PBAC score with ormeloxifene (216 to 88) was significantly more than with norethisterone (262 to 162) at 3 months (p<0.01). The rise in hemoglobin concentration and fall in endometrial thickness were also significantly more with ormeloxifene than norethisterone (7.52g% to 9.2g% vs. 7.48g% to 8.4g%, p<0.05, and 12.12mm to 9.46mm vs. 12.05mm to 10.7mm, p<0.05, respectively). Further improvement at 6 months was much more with ormeloxifene. No major side effects were reported in any group.Conclusions: Both drugs are effective in treating DUB, but ormeloxifene is superior to norethisterone in reducing menstrual blood loss.

Multi-Omic Profiling of Melophlus Sponges Reveals Diverse Metabolomic and Microbiome Architectures that Are Non-overlapping with Ecological Neighbors.

Marine sponge holobionts, defined as filter-feeding sponge hosts together with their associated microbiomes, are prolific sources of natural products. The inventory of natural products that have been isolated from marine sponges is extensive. Here, using untargeted mass spectrometry, we demonstrate that sponges harbor a far greater diversity of low-abundance natural products that have evaded discovery. While these low-abundance natural products may not be feasible to isolate, insights into their chemical structures can be gleaned by careful curation of mass fragmentation spectra. Sponges are also some of the most complex, multi-organismal holobiont communities in the oceans. We overlay sponge metabolomes with their microbiome structures and detailed metagenomic characterization to discover candidate gene clusters that encode production of sponge-derived natural products. The multi-omic profiling strategy for sponges that we describe here enables quantitative comparison of sponge metabolomes and microbiomes to address, among other questions, the ecological relevance of sponge natural products and for the phylochemical assignment of previously undescribed sponge identities

An Enhanced Bully Algorithm for Electing a Coordinator in Distributed Systems

In a distributed system for accomplishing a large complex task, the task is divided into subtask and distributed among processes and coordination among processes done via message passing. To make proper coordination and functioning we need a leader node or coordinator node which acts as a centralized control node. Leader election is the most challenging task in distributed system because it is not necessary that leader node is always same because of crash failure or out of service may occur in the system. Tremendous algorithms have been proposed for elect the new leader. These algorithms use a different technique to elect a leader in distributed system. Bully election algorithm is one of the traditional algorithms for electing a leader, in which the highest node Id is elected as a leader but this algorithm requires lots of message passing for electing a leader that imposes heavy network traffic. Due to heavy network traffic, it creates complexity in message passing and takes more time. In this paper, we introduce a new approach which overcomes the drawback of existing Bully election algorithm. Our proposed algorithm is an enhanced version of Bully election algorithm. Our analytical result shows that our algorithm is more efficient than original Bully Algorithm

Path Dependence in Disability

The average prevalence of disability in most African countries is 10% but for many it exceeds the global disability prevalence rate of 15%. The extent to which this disability capturing functional and activity limitations results in permanent job loss, lowered lifetime income, and assets, in part, depends upon the extent to which the onset of limitations becomes permanent. In this paper we use five rounds of longitudinal data from rural Malawi, a low income African country with high prevalence of disability, to examine path dependence in activity limitations. We estimate a dynamic linear panel data model where the coefficient on the one-period lagged health outcome captures path dependence in limitations. Our preferred Arellano-Bover estimates show that males experience persistence in both the incidence and intensity of severe limitations but are able to recover from all other limitations, whereas, females exhibit no significant persistence on any type of limitations. Our findings have important policy implications for computing the long-term costs associated with onsets of activity limitations as these costs can be moderated by the recovery exhibited in these limitations