Crucial Players for Inter-Organelle Communication: PI5P4Ks and Their Lipid Product PI-4,5-P2 Come to the Surface

While organelles are individual compartments with specialized functions, it is becoming clear that organellar communication is essential for maintaining cellular homeostasis. This cooperation is carried out by various interactions taking place on the membranes of organelles. The membranes themselves contain a multitude of proteins and lipids that mediate these connections and one such class of molecules facilitating these relations are the phospholipids. There are several phospholipids, but the focus of this perspective is on a minor group called the phosphoinositides and specifically, phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2). This phosphoinositide, on intracellular membranes, is largely generated by the non-canonical Type II PIPKs, namely, Phosphotidylinositol-5-phosphate-4-kinases (PI5P4Ks). These evolutionarily conserved enzymes are emerging as key stress response players in cells. Further, PI5P4Ks have been shown to modulate pathways by regulating organelle crosstalk, revealing roles in preserving metabolic homeostasis. Here we will attempt to summarize the functions of the PI5P4Ks and their product PI-4,5-P2 in facilitating inter-organelle communication and how they impact cellular health as well as their relevance to human diseases.

Architectonics of domed temples of modern Ukraine

The article highlights some results of scientific work conducted by the Institute of Architecture and Design of Lviv Polytechnic National University, Department of Fine Arts and Design, Ternopil Pedagogical University, Department of Design Architectural Environment Lviv National Agrarian University and Art TheoryVasyl Stefanyk Precarpathian National University.Scientists study the art of temple building on the territory of Ukraine. The analysis was conducted based on reliable sources - archival, publications of leading scientists, their own field research. The method of field inspections included visual inspection of sacred complexes, architectural measurements, photography, sketches, etc. The aim of the scientific work is to study the genesis of the architectural and constructive creation of the sacral dome space through the tradition of Ukrainian shrines and the development of modern trends in temple building. Tradition is one of the most important components and means of creating Ukrainian church architecture. It is an expression of national features and characteristics, its identification. The most canonical type of Ukrainian churches is the cross-domes churches, which is associated with the adoption of Christianity. This tradition is closely connected with the liturgical process and is based on a combination of Eastern and Western building traditions. In figurative and compositional expression, the dome is dominant, and tectonic accent. The architecture of dome temples depends on the capabilities of structures and building materials, which are important factors in the formation process. The authors explore the traditional ways of erecting cross-dome temples on the territory of Ukraine, which are indicative and expressive features of Ukrainian temples. An important group of dome temples are buildings created in the modern period, when architects were looking for signs of Ukrainian national style. Particularly valuable is research related to the construction of neoukrainian traditional and neoteric temples designed by Ukrainian architects. Their planning and spatial decisions directly depend on new construction materials and design solutions. Some temples are described, which are an example of innovation, but at the same time are based on national traditions. Thus, the article examines the genesis of the creation and architecture of the Ukrainian cross-domed temples. Defined peculiarities of the search for national features and identification in the Ukrainian temple building in the interwar period was determined. Highlighted contribution of modern architects and designers to the process of revival of temple building in Ukraine.

Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle

Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca2+ in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca2+ entry (SOCE) by binding to stromal interaction molecule 1 (STIM1). Abnormal SOCE and/or abnormal expression or mutations in CASQ1, STIM1, or STIM2 are associated with human skeletal, cardiac, or smooth muscle diseases. However, the functional relevance of CASQ1 along with STIM2 has not been studied in any tissue, including skeletal muscle. First, in the present study, it was found by biochemical approaches that CASQ1 is bound to STIM2 via its 92 N-terminal amino acids (C1 region). Next, to examine the functional relevance of the CASQ1-STIM2 interaction in skeletal muscle, the full-length wild-type CASQ1 or the C1 region was expressed in mouse primary skeletal myotubes, and the myotubes were examined using single-myotube Ca2+ imaging experiments and transmission electron microscopy observations. The CASQ1-STIM2 interaction via the C1 region decreased SOCE, increased intracellular Ca2+ release for skeletal muscle contraction, and changed intracellular Ca2+ distributions (high Ca2+ in the SR and low Ca2+ in the cytosol were observed). Furthermore, the C1 region itself (which lacks Ca2+-buffering ability but has STIM2-binding ability) decreased the expression of Ca2+-related proteins (canonical-type transient receptor potential cation channel type 6 and calmodulin 1) and induced mitochondrial shape abnormalities. Therefore, in skeletal muscle, CASQ1 plays active roles in Ca2+ movement and distribution by interacting with STIM2 as well as Ca2+ sensing and buffering.

CRISPR/Cas9-mediated disruption of the PYRROLIDINE KETIDE SYNTHASE gene reduces the accumulation of tropane alkaloids in Atropa belladonna hairy roots

Tropane alkaloids, including clinically important hyoscyamine and scopolamine, are produced in the roots of medicinal plant species, such as Atropa belladonna, from the Solanaceae family. Recent molecular and genomic approaches have advanced our understanding of the metabolic enzymes involved in tropane alkaloid biosynthesis. A non-canonical type III polyketide synthase (PKS), pyrrolidine ketide synthase (PYKS), catalyzes a two-step decarboxylative reaction, which involves imine-ketide condensation indispensable to tropane skeleton construction. In this study, we generated pyks mutant A. belladonna hairy roots via CRISPR/Cas9-mediated genome editing and analyzed the metabolic consequences of the loss of PYKS activity on tropane alkaloids, providing insights into a crucial role of the scaffold-forming reaction in the biosynthetic pathway.

Secretion of Pertussis Toxin from Bordetella pertussis

Production and secretion of pertussis toxin (PT) is essential for the virulence of Bordetella pertussis. Due to the large oligomeric structure of PT, transport of the toxin across bacterial membrane barriers represents a significant hurdle that the bacteria must overcome in order to maintain pathogenicity. During the secretion process, PT undergoes a two-step transport process. The first step involves transport of the individual polypeptide chains of PT across the inner membrane utilizing a generalized secretion pathway, most likely the bacterial Sec system. The second step involves the use of a specialized apparatus to transport the toxin across the outer membrane of the bacterial cell. This apparatus, which has been termed the Ptl transporter and which is unique to the PT secretion pathway, is a member of the type IV family of bacterial transporters. Here, the current understanding of the PT secretion process is reviewed including a description of the Ptl proteins that assemble to form the transporter, the general structure of type IV transporters, the known similarities and differences between canonical type IV substrate transport and Ptl-mediated transport of PT, as well as the known sequence of events in the assembly and secretion of PT.

DNASE1L3 Deficiency, New Phenotypes and Evidence for a Transient Type I Interferon Signaling

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

The optical properties of three Type II supernovae: 2014cx, 2014cy, and 2015cz

ABSTRACT We present the photometric and spectroscopic analysis of three Type II supernovae (SNe): 2014cx, 2014cy, and 2015cz. SN 2014cx is a conventional Type IIP with shallow slope (0.2 mag/50 d) and an atypical short plateau (∼86 d). SNe 2014cy and 2015cz show relatively large decline rates (0.88 and 1.64 mag/50 d, respectively) at early times before settling to the plateau phase, unlike the canonical Type IIP/L SN light curves. All of them are normal luminosity SN II with an absolute magnitude at mid-plateau of M$_{V,14\mathrm{ cx}}^{50}$=$-16.6\, \pm \, 0.4\, \rm {mag}$, M$_{V,14\mathrm{ cy}}^{50}$=$-16.5\, \pm \, 0.2\, \rm {mag}$, and M$_{V,15\mathrm{ cz}}^{50}$=$-17.4\, \pm \, 0.3\, \rm {mag}$. A relatively broad range of 56Ni masses is ejected in these explosions (0.027–0.070 M⊙). The spectra shows the classical evolution of SNe II, dominated by a blue continuum with broad H lines at early phases and narrower metal lines with P Cygni profiles during the plateau. High-velocity H i features are identified in the plateau spectra of SN 2014cx at 11 600 kms −1, possibly a sign of ejecta-circumstellar interaction. The spectra of SN 2014cy exhibit strong absorption profile of H i similar to normal luminosity events whereas strong metal lines akin to sub-luminous SNe. The analytical modelling of the bolometric light curve of the three events yields similar progenitor radii within errors (478, 507, and 660 R ⊙ for SNe 2014cx, 2014cy, and 2015cz, respectively), a range of ejecta masses (15.0, 22.2, and 20.6 M ⊙ for SNe 2014cx, 2014cy, and 2015cz), and a modest range of explosion energies (3.3–7.2 foe where 1 foe=10 51erg).

Storm types in India: linking rainfall duration, spatial extent and intensity

We examine wet events (WEs) defined from an hourly rainfall dataset based on 64 gauged observations across India (1969–2016). More than 90% of the WEs (accounting for nearly 60% of total rainfall) are found to last less than or equal to 5 h. WEs are then clustered into six canonical local-scale storm profiles (CanWE). The most frequent canonical type (CanWE#1 and #2) are associated with very short and nominal rainfall. The remaining canonical WEs can be grouped into two broad families: (i) CanWE#3 and #5 with short (usually less than or equal to 3–4 h), but very intense rainfall strongly phase-locked onto the diurnal cycle (initiation peaks in mid-afternoon) and probably related to isolated thunderstorms or small mesoscale convective clusters (MCS), and (ii) CanWE#4 and #6 with longer and lighter rainfall in mean (but not necessarily for their maximum) and more independent of the diurnal cycle, thus probably related to larger MCSs or tropical lows. The spatial extent of the total rainfall received during each CanWE, as shown by IMERG gridded rainfall, is indeed smaller for CanWE#3 and #5 than for CanWE#4 and especially #6. Most of the annual maximum 1 hour rainfalls occur during CanWE#5. Long-term trend analysis of the June–September canonical WEs across boreal monsoonal India reveals an increase in the relative frequency of the convective storm types CanWE#3 and #5 in recent years, as expected from global warming and thermodynamic considerations. This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.