Multidimensional Zonation in the Renal Vasculature

The kidneys are two bean-shaped organs located in the posterior abdominal wall. They perform the vital task of filtering the blood and concentrating its waste products into urine. As a result, the kidneys play a role in regulating blood pressure, blood pH, and electrolyte balance.4 Kidney disease is a broad heading for a variety of illnesses pertaining to the kidney, but the end result is that the kidneys have a greatly reduced ability to clean the blood.11 The overall burden of kidney disease is massive because the treatments available are extremely expensive, in short supply, and the condition itself greatly increases the chances of developing other serious conditions such as cardiovascular disease.11 The burden of kidney disease is so immense that it isrecognized a major public health issue alongside conditions such as diabetes and obesity, and there is a tremendous need for treatment options that address kidney disease in its earliest stages to prevent serious adverse health consequences down the line.11 Single cell RNA sequencing (scRNA-seq) is a new tool that enables researchers to studies tissues and organs at the resolution of individual cells.12 The technology is unique in that it enables researchers to take extremely high resolution data for thousands of cells at once, data which is then analyzed usingsophisticated bioinformatics techniques.12 In the interest in adding to the body of knowledge about the kidney and vascular systems throughout the body, I matched scRNA-seq data to an anatomical map of the renal vasculature and identified transcriptional differences between the distinct endothelial compartments, as well as identified “zonation” in the transcriptional profiles of endothelial cells along the arterio-venous axis and the cortico-medullary axis. Lastly, I compared these findings to a dataset of P0 endothelial cells, which showed an arterio-venous distribution but appeared to reveal an underdeveloped cortico-medullary axis

Care For Care-Givers - The Importance of Caregivers and the Role They Play

Many times, the incredibly difficult role of becoming a caregiver falls onto close family and friends. There is little training for the responsibilities that come along with becoming a caregiver and there is not always support for them outside family or friends. After much research and interviews with others who had been handed the role as caregiver, it is believed that while there are certain types of communication between caregivers and support groups, there should be better communication of where caregivers can turn to in order to find support. The interviews conducted for the sake of this research showed that while some caregivers who had loved ones sent home on Hospice care did receive resources for help, not all did and not all sought out outside help. This research was both informative and eye-opening. It showed that there is a bridge to gap in order to help those who are trying to find an avenue for help when they are caring for their sick loved one. After reviewing the research available, it was concluded that the importance of caregivers and the active role they play is not a well-researched topic. Caregivers are truly unsung heroes in many ways and they may not always have resources made available to them. Reaching out can sometimes be a difficult decision to make and finding a resource that fits their needs can be even more difficult. If more people were aware of how difficult being a caregiver can be and how much it can take to be a caregiver, many people may want to educate themselves more on how they can help a caregiver or how they can help a caregiver seek out resources to benefit them during their journey

Experience of depression in older adults with and without a physical long-term condition: findings from a qualitative interview study

OBJECTIVE: To understand how the lived experience of depression differs among patients with a long-term condition (LTC) compared with those without an LTC, and how the experience differs across different types of LTC. DESIGN: Face-to-face, semistructured interviews. SETTING: Primary care; General Practitioner (GP) surgeries in and around North London. PARTICIPANTS: 41 primary care patients with depression were recruited. Our sample comprised participants aged 55–75 years with depression only (n=12), depression and coronary heart disease (n=5), depression and type 2 diabetes (n=10) and depression and arthritis (n=14). RESULTS: Interviews were conducted, audio recorded, transcribed and analysed using thematic analysis. The results revealed that the cardinal diagnostic symptoms of depression (anhedonia, sadness) were experienced by all our participants regardless of LTC. However, the LTC did interact with depression by compounding somatic, cognitive and emotional symptoms, increasing disability and reducing independence, and hindering attempts at coping with mental illness. Our findings demonstrate common experiences across patients as well as key differences based on LTC. CONCLUSIONS: We suggest four key implications for future care practices of these patients: (1) not all participants with depression and LTC view their mental and physical health as interconnected; there should be allowances in care plans for separate treatment pathways; (2) key features of depression that affect LTC management are social withdrawal and lack of motivation to self-manage or access healthcare; (3) key features of LTCs that worsen depression are pain, the unpredictability of future health and progressive disability; (4) positive self-management of LTC could improve self-efficacy and therefore mood, and should be encouraged

Melanocortin 1 receptor targeted imaging of melanoma with gold nanocages and positron emission tomography

Purpose: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. Method: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. Results: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. Conclusion: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics. </jats:sec

Impact of tyrosine phosphorylation of Syntaxin 4 and Munc18c on GLUT4 translocation

Insulin is an important regulator of glucose homeostasis. Insulin stimulation of fat and muscle cells results in the rapid translocation of the glucose transporter GLUT4 to the plasma membrane from its intracellular stores, allowing uptake of glucose into the cells from the blood. This tethering, docking and fusion event is driven by the formation of a SNARE complex at the plasma membrane consisting of the t-SNAREs Syntaxin4 (Sx4) and SNAP23 and the v-SNARE VAMP2. The formation of this complex is regulated by the SM protein Munc18c. It has been shown that Sx4 is phosphorylated at residues Y115 and Y251 following insulin stimulation; however the effects of these phosphorylation events have yet to be studied. In addition phosphorylation of Y521 in Munc18c is also increased following insulin stimulation. This study aimed to first elucidate the effects of Sx4 phosphorylation on SNARE protein interactions and GLUT4 trafficking, then to begin to examine the impact of phosphorylation of both Sx4 and Munc18c. I have used an in vitro approach to assess the affect Sx4 phosphorylation has on SNARE complex assembly. I have shown, using phospho-mimetic recombinant proteins, that the phosphorylation state of Sx4 affects the rate of SNARE complex assembly and its binary interactions with VAMP2 and SNAP23. Moreover, that this may be due to a conformational change in the protein. I have also shown, for the first time, that it is likely that Sx4 can be phosphorylated on Y115 and Y251 simultaneously. In addition I have used a HA-GLUT4-GFP expressing HeLa cell line to show that expression of phospho- mimetic Sx4 increases translocation of GLUT4 to the PM under basal conditions. Finally, I have begun to investigate the implications of both Sx4 and Munc18c phosphorylation on their in vitro interactions. This data provides insights into the direct regulation of membrane trafficking proteins by the insulin-signalling pathway. Increased understanding of the regulation of GLUT4 translocation could help to develop future therapies for type 2 diabetes, where GLUT4 trafficking is impaired

Mining morphometrics and age from past survey photographs

Abstract Background Researchers often document wildlife surveys using images. These images contain data that can be used to understand alterative research objectives, even years after they were originally captured. We have developed a method to measure age and morphology (body size measurements and tusk size) from survey image databases and future surveys, without the availability of a known subject distance or a scale in each image. African savanna elephants (Loxodonta africana) serve as an ideal model species to develop a non-invasive, image-based morphometric methodology: as handling these animals is particularly invasive and expensive, involving anaesthesia and because of their IUCN ‘vulnerable’ status. We compare in situ measurements, taken during collaring events, to tusk-to-body-size ratios, measured from the images. Results We provide evidence that relative morphological measurements, musth timing, and age of male African savanna elephants can accurately be obtained from a survey image database of over 30,000 images, taken over an 18-year period. Of the 11 tusk to body size ratios calculated, we recommend the use of two in particular for future measurement in African elephants to determine size and age: 1) tusk length to tusk diameter and 2) tusk length to body height. Conclusions We present a practical, non-invasive measure to estimate morphometrics, including both age and tusk size from photographs, which has conservation applications to the protection of elephants and is relevant to a range of other taxa

Mining morphometrics and age from past survey photographs

Background Researchers often document wildlife surveys using images. These images contain data that can be used to understand alterative research objectives, even years after they were originally captured. We have developed a method to measure age and morphology (body size measurements and tusk size) from survey image databases and future surveys, without the availability of a known subject distance or a scale in each image. African savanna elephants (Loxodonta africana) serve as an ideal model species to develop a non-invasive, image-based morphometric methodology: as handling these animals is particularly invasive and expensive, involving anaesthesia and because of their IUCN ‘vulnerable’ status. We compare in situ measurements, taken during collaring events, to tusk-to-body-size ratios, measured from the images. Results We provide evidence that relative morphological measurements, musth timing, and age of male African savanna elephants can accurately be obtained from a survey image database of over 30,000 images, taken over an 18-year period. Of the 11 tusk to body size ratios calculated, we recommend the use of two in particular for future measurement in African elephants to determine size and age: 1) tusk length to tusk diameter and 2) tusk length to body height. Conclusions We present a practical, non-invasive measure to estimate morphometrics, including both age and tusk size from photographs, which has conservation applications to the protection of elephants and is relevant to a range of other taxa

Sistem Hirarki Kelembagaan Badan Pengelola Zakat di Indonesia (Tinjauan terhadap Pelaksanaan Undang-undang No. 23 Tahun 2011)

: Government support for the existence and role of zakat management organization indicated by the issuance of legislation on the management of zakat that Act No. 38 of 1999 and the decision of the Minister of Religion No. 581 of 1999 on the implementation of Act No. 38 of 1999 which was amended by Act No. 23 of 2011 concerning the management of zakat. Many factors of causing non-optimal zakat as legislation, mostly related to the system and institutional factors. In this case, should the government as well as amil zakat organization has a strategic role to establish an institutional system of zakat and charity empowerment and support the establishment of the implementation of the charity as a binding regulation. This can occur if the control system of zakat management organization operating effectively, as well as the existence of legislation on the management of zakat either No. 38 of 1999 and No. 23 of 2011. In other words, the optimization of the implementation of zakat is affected by the system and the effective management of zakat management in addition to firmness of government in enforcing the implementation of zakat either written in the legislation and are implementable in order to achieve good governance zakat (alms good governance)