Allelic Polymorphism of GIGANTEA is Responsible for Naturally Occurring Variation in Circadian Period in Brassica Rapa

GIGANTEA (GI) was originally identified by a late-flowering mutant in Arabidopsis, but subsequently has been shown to act in circadian period determination, light inhibition of hypocotyl elongation, and responses to multiple abiotic stresses, including tolerance to high salt and cold (freezing) temperature. Genetic mapping and analysis of families of heterogeneous inbred lines showed that natural variation in GI is responsible for a major quantitative trait locus in circadian period in Brassica rapa. We confirmed this conclusion by transgenic rescue of an Arabidopsis gi-201 loss of function mutant. The two B. rapa GI alleles each fully rescued the delayed flowering of Arabidopsis gi-201 but showed differential rescue of perturbations in red light inhibition of hypocotyl elongation and altered cold and salt tolerance. The B. rapa R500 GI allele, which failed to rescue the hypocotyl and abiotic stress phenotypes, disrupted circadian period determination in Arabidopsis. Analysis of chimeric B. rapa GI alleles identified the causal nucleotide polymorphism, which results in an amino acid substitution (S264A) between the two GI proteins. This polymorphism underlies variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Loss-of-function mutations of B. rapa GI confer delayed flowering, perturbed circadian rhythms in leaf movement, and increased freezing and increased salt tolerance, consistent with effects of similar mutations in Arabidopsis. Collectively, these data suggest that allelic variation of GI—and possibly of clock genes in general—offers an attractive target for molecular breeding for enhanced stress tolerance and potentially for improved crop yield

Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization

The serpins (serine proteinase inhibitors) are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Serpins play absolutely critical role in the control of proteases involved in the inflammatory, complement, coagulation and fibrinolytic pathways and are associated with many conformational diseases. Serpin's native state is a metastable state which transforms to a more stable state during its inhibitory mechanism. Serpin in the native form is in the stressed (S) conformation that undergoes a transition to a relaxed (R) conformation for the protease inhibition. During this transition the region called as reactive center loop which interacts with target proteases, inserts itself into the center of β-sheet A to form an extra strand. Serpin is delicately balanced to perform its function with many critical residues involved in maintaining metastability. However due to its typical mechanism of inhibition, naturally occurring serpin variants produces conformational instability that allows insertion of RCL of one molecule into the β-sheet A of another to form a loop-sheet linkage leading to its polymerization and aggregation. Thus understanding the molecular basis and amino acid involved in serpin polymerization mechanism is critical to devising strategies for its cure

Human Immunodeficiency Virus -1 and Hepatitis B Virus Co-Infections among Injecting Drug Users in Malindi, Kenya

Currently no published data addressing the burden of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) co-infection among injecting drug users (IDUs) in Kenya exists. These two viruses share similar routes of transmission, with illicit drug use by injection being the major route of infection. Injecting drug use is a rapidly growing problem in coastal towns of Kenya and the problem is aggravated by sex tourism.This study aimed at determining the prevalence of HBV in HIV positive IDUs and correlating the findings with socio-demographic factors of the study population.A cross-sectional study was conducted using structured questionnaires and laboratory testing of blood samples. Surface antigens for HBV (HBsAg) and anti-HIV antibodies were screened using rapid kits followed by Enzyme Linked Immunosorbent assay tests on positive samples using Hepanostika and Vironostika test kits, for HIV and HBV, respectively. The CD4+ T-cell count was determined by flow cytometry.The prevalence of HIV/HBV co-infection was 14.3% (13/91) with a mean age of 33.2 (SD ± 8.1) years. The mean CD4+ cell count in the HIV/HBV co-infected individuals was significantly lower than HIV mono-infection. Needle sharing and duration of active injection of drugs were significantly associated with HIV/HBV co-infections.This study concludes a potentially high prevalence of HBV/ HIV co-infection in injecting drug users in Malindi, Kenya. With limited evidence on IDU prevalence and its consequences in sub-Saharan Africa, the results of this study highlight the need for a more refined policy on HIV treatment strategy among IDUs. There is a further need for triple testing for HIV, HBV and HCV among suspected IDUs and other associated risk groups like the commercial sex workers before commencement of treatment. Keywords: Injecting drug users, HIV-1, HBV, viral co-infection, Malindi, Keny

Assessment of Risk Predisposition to Human Papilloma Virus through Cervical Infections Screening of Women Attending an Outpatient Health Facility in Nairobi, Kenya

There is limited data on comparative disposition to cervical cancer among HPV infected women in Kenya. We aimed to determine the distribution of HPV infection, cervical abnormalities and infections commonly reported on cervical pap smears among both HIV positive and HIV negative women attending a reproductive health clinic at the largest national hospital in Kenya. A total of 187 women aged 18 to 50 years attending the reproductive clinic at Kenyatta National Referral Hospital in Nairobi were recruited into the study. All consenting subjects were screened for HIV by serology and their cervical smears taken and immediately fixed on slides for Papanicolaou (Pap) staining. A second endocervical swab was collected in the same sitting for HPV DNA extraction and PCR amplification of the HPV LI region.  Of the 187 women studied, 27 (14.4 %) were positive for HIV and 90 (48.1%) had one or more infection associated with bacterial vaginosis, candidiasis, cervicitis or inflammation of the cervix of unknown cause.  Eight (4.3%) women had abnormal cervix, 3/8 being of high grade squamous intraepithelial lesions (HSIL), 1/8 of low grade squamous intraepithelial lesions (LSIL), 1/8 had adenocarcinoma while the remaining 3 had atypical squamous cells of undetermined significance (ASC-US). The remaining 89/187 (47.6%) women had normal smears with no infection. Of the 89 women with normal smears, 82 (92.1%) were HIV negative.  A total of 66 (35.3%) women were positive for HPV L1 DNA by PCR and included 30 of the 89 women with normal cytology. Of the 27 HIV positive women, 14 (51.9%) were also positive for HPV LI DNA. 52 of the 160 (32.5%) HIV negative women were positive for HPV L1 DNA. We report more cases of cervical intraepithelial lesions among HIV positive than HIV negative women. Similarly, the other infections commonly found on Pap smear tests were higher among HIV negative than HIV positive women. HPV prevalence among these clinic-attending women was higher in those with normal cytology, indicating an increased underlying risk of cervical cancer in a setting where routine diagnostic screening is limited or non-existent. Keywords: cervical cancer, HIV, HPV, cervical cytolog

The role of facilities management in fighting COVID-19 outbreak: Evidence from Malaysian public hospitals

The aim of this study is to provide a holistic review of the fight against COVID-19 in developing countries, particularly Malaysia. Specifically, the study aims to determine how facilities management delivery in public hospitals can be improved to ensure readiness in handling COVID-19 cases. We conducted a review of the literature and reliable media updates on COVID-19 and services management. A critical synthesis of COVID-19 information was conducted to scrutinise the technical aspects and highlight how facilities management can be improved to ensure hospital readiness in managing COVID-19 cases. The data and information used in the present study were collected up to the time of writing this paper, which leaves a room for further studies. Nonetheless, this study’s recommendations are useful for understanding the present and future pandemics. This study is a first attempt to summarise the data on facilities management in relation to the COVID-19 pandemic in the Malaysian context. The study’s findings are suitable for the developing countries in managing healthcare management practices in the fight against COVID-19. This study aims to highlight current issues in order to provide a more objective assessment of facilities management to ensure hospital readiness in handling COVID-19 cases

An evaluation of cots-based radar for very small drone sense and avoid application

The use of very small unmanned aerial vehicles (UAVs) are increasingly common these days but its applications are limited to the pilot line-of-sight view. To extend its use beyond the pilot view, UAVs need to be equipped sense and avoid (SAA) system to avoid potential collisions. However, the development of SAA for very small drones is still in the infancy stage mainly due to the high cost of design and development for reliable range sensors. Recent developments of very small size and lightweight commercial off-the-shelf (COTS)-based radar systems may become a crucial element in very small drone applications. These types of radars are primarily developed for industrial sensing but can be adapted for applications such SAA. Thus, this paper contributes to the survey of a miniature and lightweight radar sensor to assist the SAA development. The focus of this paper is to analyse the eligibility of a COTS-based radar in detecting very small drones. For this purpose, we used a frequency-modulated continuous radar (FMCW) developed by Infineon Technologies. Field test results show the real-time capability of the radar sensor to detect the very small drones within ± 0.5 meters in static and dynamic conditions

HIV-1 Coreceptor Tropism among Kenyans Under Highly Active Antiretroviral Therapy.

Despite the scale up of the use of combined highly active antiretroviral (ARV) therapy, many HIV-1 infected patients are still failing treatment in Kenya. In 2007, the Food Drug and Administration (FDA) approved the use of CCR5 antagonists in treatment experienced patients. CCR5 antagonists work by inhibiting the entry of HIV-1 that uses CCR5 as a coreceptor to gain entry into cells. CCR5 59029 A/G (promoter region—rs1799987) is a polymorphism that leads to the upregulation of the expression of the CCR5 protein thereby affecting the rate of HIV-1 infection. The use of these CCR5 antagonists in Kenya is limited partly because of minimal data on host genetics and coreceptor tropism among HIV-1 infected patients. In this study, we aimed at determining the prevalence of CCR5 tropic variants and CCR5 59029AG promoter polymorphism known to influence HIV-1 infection. We sequenced the V3 region of the env gene and inferred the HIV-1 tropism using clonal model of Geno2Pheno algorithm (FPR= 5%).   Also, we assessed the frequency of the CCR5 promoter polymorphisms among the patients by sequencing the polymorphic region of the CCR5 promoter. Majority of the patients (77.27%) had R5 tropic viruses whereas 22.73% of the study subjects had detectable CCR4 using viruses. The frequencies of the CCR5 59029 AA, AG, and GG genotypes were 14 (31.82%), 9 (20.45%) and 21(47.73%), respectively. Taken together, these results indicate that CCR5 antagonists could have potential therapeutic effects in the clinical management of HIV-1 among the infected patients in Kenya. Key words: CCR5 antagonists, CCR5 59029AG, HAART, HIV-1, Polymorphism, Tropis

TsHKT1;2, a HKT1 homolog from the extremophile arabidopsis relative Thellungiella salsuginea, shows K \u3csup\u3e+\u3c/sup\u3e specificity in the presence of NaCl

Cellular Na +/K + ratio is a crucial parameter determining plant salinity stress resistance. We tested the function of plasma membrane Na +/K + cotransporters in the High-affinity K + Transporter (HKT) family from the halophytic Arabidopsis (Arabidopsis thaliana) relative Thellungiella salsuginea. T. salsuginea contains at least two HKT genes. TsHKT1;1 is expressed at very low levels, while the abundant TsHKT1;2 is transcriptionally strongly up-regulated by salt stress. TsHKT-based RNA interference in T. salsuginea resulted in Na + sensitivity and K + deficiency. The athkt1 mutant lines overexpressing TsHKT1;2 proved less sensitive to Na + and showed less K + deficiency than lines overexpressing AtHKT1. TsHKT1;2 ectopically expressed in yeast mutants lacking Na + or K + transporters revealed strong K + transporter activity and selectivity for K + over Na +. Altering two amino acid residues in TsHKT1;2 to mimic the AtHKT1 sequence resulted in enhanced sodium uptake and loss of the TsHKT1;2 intrinsic K + transporter activity. We consider the maintenance of K + uptake through TsHKT1;2 under salt stress an important component supporting the halophytic lifestyle of T. salsuginea. © 2012 American Society of Plant Biologists

A single amino-acid substitution in the sodium transporter HKT1 associated with plant salt tolerance

© 2016 American Society of Plant Biologists. All rights reserved. A crucial prerequisite for plant growth and survival is the maintenance of potassium uptake, especially when high sodium surrounds the root zone. The Arabidopsis HIGH-AFFINITY K+ TRANSPORTER1 (HKT1), and its homologs in other salt-sensitive dicots, contributes to salinity tolerance by removing Na+ from the transpiration stream. However, TsHKT1;2, one of three HKT1 copies in Thellungiella salsuginea, a halophytic Arabidopsis relative, acts as a K+transporter in the presence of Na+ in yeast (Saccharomyces cerevisiae). Amino-acid sequence comparisons indicated differences between TsHKT1;2 and most other published HKT1 sequences with respect to an Asp residue (D207) in the second pore-loop domain. Two additional T. salsuginea and most other HKT1 sequences contain Asn (N) in this position. Wild-type TsHKT1;2 and altered AtHKT1 (AtHKT1N-D) complemented K+-uptake deficiency of yeast cells. Mutanthkt1-1 plants complemented with both AtHKT1N-D and TsHKT1;2 showed higher tolerance to salt stress than lines complemented by the wild-type AtHKT1. Electrophysiological analysis in Xenopus laevis oocytes confirmed the functional properties of these transporters and the differential selectivity for Na+ and K+based on the N/D variance in the pore region. This change also dictated inward-rectification for Na+ transport. Thus, the introduction of Asp, replacing Asn, in HKT1-type transporters established altered cation selectivity and uptake dynamics. We describe one way, based on a single change in a crucial protein that enabled some crucifer species to acquire improved salt tolerance, which over evolutionary time may have resulted in further changes that ultimately facilitated colonization of saline habitats

Effects of the COVID-19 pandemic on the management of ST-Segment elevation myocardial infarction in Indonesia: a cohort study [version 1; peer review: 2 approved]

Background: ST-segment elevation myocardial infarction (STEMI) is a form of acute coronary syndrome with high mortality rate. Management of STEMI should be performed as soon as possible to prevent further damage. With the emergence of coronavirus disease 2019 (COVID-19), it may face obstacles. To overcome those problems, some changes in policy focusing on fibrinolytic therapy in STEMI patients have been applied. This study aimed to identify the effects of COVID-19 in management of STEMI patients in Indonesia. Methods: This retrospective study was conducted in Dr. Cipto Mangunkusumo Hospital (CMH), the national referral center in Indonesia. We compared data between 2018 to 2019 and 2020 to 2021 as before and during COVID-19 pandemic period, respectively. We analyzed the effects of COVID-19 on STEMI patients' visits to hospital i.e., monthly hospital admission and symptoms-to-hospital, management of STEMI i.e., the strategies and time of reperfusion, and clinical outcomes of STEMI patients i.e., major adverse coronary event and mortality. Results: There was a significant statistically reduced mean of monthly hospital admissions from 11 to 7 (p = 0.002) and prolonged duration of symptoms-to-hospital during COVID-19 from 8 to 12 hours (p = 0.005). There was also a decrease in primary percutaneous coronary intervention (PPCI) procedures during COVID-19 (65.2% vs. 27.8%, p<0.001), which was accompanied by an increased number of fibrinolytic (1.5% vs. 9.5%, p<0.001) and conservative therapy (28.5% vs. 55.6%, p <0.01). Moreover, there was also a prolonged duration of diagnosis-to-wire-crossing time (160 vs. 186 minutes, p = 0.005), meanwhile, percentage of urgent PCI, door-to-needle time, and clinical outcomes were not statistically significant. Conclusions: During COVID-19 pandemic, the number STEMI patients declined in monthly hospital admission, delays in symptoms-to-hospital time, changes in type of reperfusion strategy, and delays in PPCI procedures in CMH. Meanwhile, fibrinolytic time and clinical outcomes were not affected