KAJIAN KEBUTUHAN INTEGRASI LAYANAN ANGKUTAN UMUM MASSAL DI KOTA SEMARANG DAN SEKITARNYA

Angkutan umum massal berbasis jalan telah dikembangkan oleh Pemerintah Kota Semarang sejak tahun 2009 hingga kini (Trans Semarang). Disisi lain, Pemerintah Provinsi Jawa Tengah sejak tahun 2017 juga melakukan hal yang sama di Wilayah Aglomerasi Kedungsepur (Trans Jateng). Namun terkesan berjalan sendiri-sendiri dan terjadi tumpang tindih layanan di ruas-ruas jalan tertentu. Dengan demikian, perlu dilakukan penelitian kebutuhan pengintegrasian layanan angkutan umum massal di Kota Semarang dan sekitarnya. Penelitian ini menggunakan pendekatan kuantitatif dengan analisis statistik deskriptif dan analisis spasial untuk mengetahui karakteristik dan pola permintaan perjalanan penggunanya. Hasil penelitian ini menunjukkan bahwa pengguna Koridor 1 dan 2 Trans Semarang dari luar Kota Semarang mencapai 39,14% dan 60,86% berasal dari dalam Kota Semarang. Pengguna dengan tujuan ke luar Kota Semarang mencapai 42,23% dan 57,77% tujuan di dalam Kota Semarang. Hal ini membuktikan bahwa Koridor 1 dan 2 mengakomodasi penumpang yang asal tujuannya cukup besar dari luar Kota Semarang. Terdapat tumpang tindih layanan mencapai 60% dari panjang lintasan di Koridor 1 Trans Jateng dan Koridor 2 Trans Semarang. Moda first mile pengguna Koridor 2 didominasi oleh Trans Jateng sebesar 51,51% dan last mile didominasi oleh penggunaan motor sebesar 48,10%. Penelitian ini menyarankan bahwa rute layanan Trans Jateng kedepannya dapat mengakomodir permintaan perjalanan di dalam kawasan penyangga dengan konsep layanan loop (mengelilingi), berbeda dari kondisi saat ini. Selanjutnya, layanan Trans Jateng yang menuju ke Kota Semarang dapat berhenti di titik perbatasan, dimana pergerakan kemudian dilayani oleh Trans Semarang dan diharapkan dapat memberikan layanan yang lebih baik kepada masyarakat di Kota Semarang dan sekitarnya.

Application of CRISPR/Cas9 editing and digital droplet PCR in human iPSCs to generate novel knock-in reporter lines to visualize dopaminergic neurons

Human induced pluripotent stem cells (hiPSCs) have become indispensable for disease modelling. They are an important resource to access patient cells harbouring disease-causing mutations. Derivation of midbrain dopaminergic (DAergic) neurons from hiPSCs of PD patients represents the only option to model physiological processes in a cell type that is not otherwise accessible from human patients. However, differentiation does not produce a homogenous population of DA neurons and contaminant cell types may interfere with the readout of the in vitro system. Here, we use CRISPR/Cas9 to generate novel knock-in reporter lines for DA neurons, engineered with an endogenous fluorescent tyrosine hydroxylase \u2013 enhanced green fluorescent protein (TH-eGFP) reporter. We present a reproducible knock-in strategy combined with a highly specific homologous directed repair (HDR) screening approach using digital droplet PCR (ddPCR). The knock-in cell lines that we created show a functioning fluorescent reporter system for DA neurons that are identifiable by flow cytometry

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β

Accumulation of amyloid-β (Aβ1-42) is a key event mediating the cognitive deficits in Alzheimer’s disease (AD) as Aβ promotes synaptic dysfunction and triggers neuronal death. Recent evidence has linked the hormone leptin to AD as leptin levels are markedly attenuated in AD patients. Leptin is also a potential cognitive enhancer as it facilitates the cellular events underlying hippocampal learning and memory. Here we show that leptin prevents the detrimental effects of Aβ1-42on hippocampal long-term potentiation (LTP). Moreover leptin inhibits Aβ1-42-driven facilitation of long-term depression (LTD) and internalization of the AMPA receptor subunit, GluR1, via activation of PI3-kinase. Leptin also protects cortical neurons from Aβ1-42-induced cell deathby a STAT-3-dependent mechanism. Furthermore, leptin inhibits Aβ1-42-mediated upregulation of endophilin I and phosphorylated tau (p-tau) in vitro, whereas cortical levels of endophilin I and p-tau are enhanced in leptin-insensitive Zucker fa/fa rats. Thus leptin benefits the functional characteristics and viability of neurons that degenerate in AD. These novel findings establish that the leptin system is an important therapeutic target in neurodegenerative conditions