Everybody needs sphingolipids, right!:Mining for new drug targets in protozoan sphingolipid biosynthesis

Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.<br/

Aerobic Exercise Treatment Model as an Attempt to Improve Promotif and Preventive Functions of Pulmonary Capacity

Pulmonary function respiration system as important in the human body, the function provides oxygen (O2) from the outside of the body for the process of cell metabolism and removing carbon dioxide (CO2) and water (H2O) from the body. Function lung capacity is influenced by genetic, age, gender, height, pulmonary disease, smoking habit and custom of the sport. Aerobic exercises are done routinely run will cause the change form on the muscular system, circulatory system, cardiovascular system and ability of lung capacity function.  Response to aerobic exercise against pulmonary function capacity depending on exercise intensity, duration and frequency of exercise. The purpose of this research is to know the influence of aerobic exercise against pulmonary function capacity. This research is Experimental Quasy Study, with design of Pretest-Posttest with control group design. The sample amounted to 35 people. The results of the statistical analysis show that there is a significant influence of aerobic exercise to increased lung capacity function. The mean FVC after sports increased 1, 10% with p value = 0,017 and average FEV1 after sports increased 0, 23% with p value = 0,005. Time duration of exercise indicates the absence of effect on the changes in pulmonary function capacity (FVC p value = 0,494 and FEV1 p value = 0,805). Frequency of exercise 3 times a week showed the existence of significant influence towards increasing lung capacity function (FVC p value = 0,001 and  FEV1 p value = 0,000). Key words: aerobic Exercise, time duration, frequency, FVC (Forced Vital Capacity), FEV1 (Forced Expiratory Volume in One Second

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards

Perancangan Integrated Marketing Communication Total Buah Segar Surabaya

Meningkatnya konsumsi buah di Kota Surabaya menyebabkan persaingan bisnis retail buah segar semakin memanas. Berdasarkan potensi permintaan konsumsi buah yang diperoleh dari data Badan Pusat Statistik, maka Total Buah Segar membuka cabang di jl.Tunjungan no.1 Surabaya.Diharapkan pembukaan Total Buah Segar Surabaya dapat memberikan profit optimal.Tidak adanya strategi promosi yang dilakukan oleh Total Buah Segar Surabaya, membuat Total Buah Segar Surabaya mengalami kesulitan dalam memasuki pangsa pasar Kota Surabaya.Metode yang digunakan untuk membantu menyelesaikan permasalahan tersebut adalah Integrated Marketing Communicatio

Differential localization and expression of complement in a rat model of motor neuron disease

ComBio is the major ASBMB conference held each year, in association with other organisations. This page has links to past, current and future ComBio meetings. Further information and links will be placed online as they become available

Genome deletions to overcome the directed loss of gene function in Leishmania

With the global reach of the Neglected Tropical Disease leishmanaisis increasing, coupled with a tiny armoury of therapeutics which all have problems with resistance, cost, toxicity and/or administration, the validation of new drug targets in the causative insect vector borne protozoa Leishmania spp is more important than ever. Before the introduction of CRISPR Cas9 technology in 2015 genetic validation of new targets was carried out largely by targeted gene knockout through homologous recombination, with the majority of genes targeted (~70%) deemed non-essential. In this study we exploit the ready availability of whole genome sequencing technology to reanalyse one of these historic cell lines, a L. major knockout in the catalytic subunit of serine palmitoyltransferase (LCB2), which causes a complete loss of sphingolipid biosynthesis but remains viable and infective. This revealed a number of Single Nucleotide Polymorphisms, but also the complete loss of several coding regions including a gene encoding a putative ABC3A orthologue, a putative sterol transporter. Hypothesising that the loss of such a transporter may have facilitated the directed knockout of the catalytic subunit of LCB2 and the complete loss of de novo sphingolipid biosynthesis, we re-examined LCB2 in a L. mexicana line engineered for straightforward CRISPR Cas9 directed manipulation. Strikingly, LCB2 could not be knocked out indicating essentiality. However, simultaneous deletion of LCB2 and the putative ABC3A was possible. This indicated that the loss of the putative ABC3A facilitated the loss of sphingolipid biosynthesis in Leishmania, and suggested that we should re-examine the many other Leishmania knockout lines where genes were deemed non-essential

On the Prediction of Extreme Ecological Events

Ecological studies often focus on average effects of environmental factors, but ecological dynamics may depend as much upon environmental extremes. Ecology would therefore benefit from the ability to predict the frequency and severity of extreme environmental events. Some extreme events (e.g., earthquakes) are simple events: either they happen or they don\u27t, and they are generally difficult to predict. In contrast, extreme ecological events are often compound events, resulting from the chance coincidence of run-of-the-mill factors. Here we present an environmental bootstrap method for resampling short-term environmental data (rolling the environmental dice) to calculate an ensemble of hypothetical time series that embodies how the physical environment could potentially play out differently. We use this ensemble in conjunction with mechanistic models of physiological processes to analyze the biological consequences of environmental extremes. Our resampling method provides details of these consequences that would be difficult to obtain otherwise, and our methodology can be applied to a wide variety of ecological systems. Here, we apply this approach to calculate return times for extreme hydrodynamic and thermal events on intertidal rocky shores. Our results demonstrate that the co-occurrence of normal events can indeed lead to environmental extremes, and that these extremes can cause disturbance. For example, the limpet Lottia gigantea and the mussel Mytilus californianus are co-dominant competitors for space on wave-swept rocky shores, but their response to extreme environmental events differ. Limpet mortality can vary drastically through time. Average yearly maximum body temperature of L. gigantea on horizontal surfaces is low, sufficient to kill fewer than 5% of individuals, but on rare occasions environmental factors align by chance to induce temperatures sufficient to kill \u3e99% of limpets. In contrast, mussels do not exhibit large temporal variation in the physical disturbance caused by breaking waves, and this difference in the pattern of disturbance may have ecological consequences for these competing species. The effect of environmental extremes is under added scrutiny as the frequency of extreme events increases in response to anthropogenically forced climate change. Our method can be used to discriminate between chance events and those caused by long-term shifts in climate