A systems-biology approach to understanding the ciliopathy disorders.

'Ciliopathies' are an emerging class of genetic multisystemic human disorders that are caused by a multitude of largely unrelated genes that affect ciliary structure/function. They are unified by shared clinical features, such as mental retardation, cystic kidney, retinal defects and polydactyly, and by the common localization of the protein products of these genes at or near the primary cilium of cells. With the realization that many previously disparate conditions are a part of this spectrum of disorders, there has been tremendous interest in the function of cilia in developmental signaling and homeostasis. Ciliopathies are mostly inherited as simple recessive traits, but phenotypic expressivity is under the control of numerous genetic modifiers, putting these conditions at the interface of simple and complex genetics. In this review, we discuss the ever-expanding ciliopathy field, which has three interrelated goals: developing a comprehensive understanding of genes mutated in the ciliopathies and required for ciliogenesis; understanding how the encoded proteins work together in complexes and networks to modulate activity and structure-function relationships; and uncovering signaling pathways and modifier relationships

Inherited Neurodevelopmental Brain Diseases: Applications of Homozygosity Mapping to Identify New Genetic Causes of Disease

AbstractObjectiveThe last two decades have seen major advancements in our understanding of some of the most common neurodevelopmental disorders in the field of child neurology. However, in the majority of individual patients, it is still not possible to arrive at a molecular diagnosis, due in part to lack of knowledge ofmolecular causes of these tremendously complex conditions. Common genetic disorders of brain development include septo-optic dysplasia, schizencephaly, holoprosencephaly, lissencephaly and hindbrain malformations. For each of these disorders, a critical step in brain development is disrupted. Specific genetic diagnosis is now possible in some patients with most of these conditions. For the remaining patients, it is possible to apply gene-mapping strategies using newly developed high-density genomic arrays to clone novel genes. This is especially important in countries like Iran where large family size and marriage between relatives makes these strategies tremendously powerful

Ohio Workers and the COVID-19 Global Health Emergency

The global economy has never before experienced the scale of sudden economic shock that is now underway. This is unchartered territory. Although the U.S. has many economic policies and worker support programs designed to ease dislocation during recessions, these programs were not designed for the unique circumstances of this global pandemic. The most important program for workers is Unemployment Insurance. The first chart in this report shows the unprecedented number of new applications for unemployment insurance filed by Ohio workers during the week of March 16th. If all applicants are awarded benefits, the second chart shows that the number of Ohio workers receiving benefits is solidly on course to surpass the peak that occurred after 9-11 in 2001, and soon could exceed the peak that was experienced in 2008 during the Great Recession

Before The New Street: Opportunity Corridor Residents and Jobs, 2017

The Ohio Department of Transportation is constructing the final portion of “the Opportunity Corridor.” This new 4-6 lane city street in Cleveland will connect I-490 at the 55th Street exit to University Circle by way of 105th Street, which was extended as part of this multi-stage project. The new street will improve commute times for University Circle workers and improve access to the distressed neighborhoods along its path

Before The New Street: Opportunity Corridor Residents and Jobs, 2017

The Ohio Department of Transportation is constructing the final portion of “the Opportunity Corridor.” This new 4-6 lane city street in Cleveland will connect I-490 at the 55th Street exit to University Circle by way of 105th Street, which was extended as part of this multi-stage project. The new street will improve commute times for University Circle workers and improve access to the distressed neighborhoods along its path

The Potential Impacts of Working from Home on Post COVID-19 Municipal Wage Tax Revenues in Ohio

Every nation evolves its own complex system to collect taxes to finance government operations. No two systems are exactly alike. Each is embedded in a unique blend of historical, cultural, economic, and political factors at the national, sub-national, and local levels. All adjust themselves continuously to changes that occur in their internal and external environments. The COVID-19 pandemic has been a major disruptive external shock to the status quo of every tax system throughout the world. Most systems responded to the crisis with short-term measures designed to reduce uncertainty and to maintain as much flow of tax revenues as possible. Yet the COVID-19 pandemic is changing many of the long-established patterns of cultural, economic, and political behaviors on which tax systems are based. Some behavioral changes may be transitory. Yet many will persist, at least in some fashion. Persistent changes could invalidate important assumptions about behavior that have been used to create and manage each specific tax system. Working from home is one behavior that has important consequences for some tax systems. This paper examines one example

Using whole rock and in situ pyrite chemistry to evaluate authigenic and hydrothermal controls on trace element variability in a Zn mineralized Proterozoic subbasin

The mid-Proterozoic stratigraphy of the McArthur Basin (Australia) contains some of the most well-preserved sedimentary rocks of Precambrian age, which are also host to giant, clastic dominant (CD-type) massive sulfide Zn deposits. The most recently discovered CD-type deposit (the Teena deposit) is located in the Teena subbasin and hosted by the 1.64 Ga Barney Creek Formation. The Teena subbasin, therefore, provides the perfect natural laboratory for evaluating authigenic and hydrothermal controls on trace element (TE) variability, both of which contribute to paleoenvironmental reconstructions and ore deposit models. As the Teena deposit formed beneath the paleoseafloor, this also provides the opportunity to evaluate TE zonation around a fossilized subseafloor replacement hydrothermal system. In situ laser ablation inductively coupled mass spectrometry (LA-ICP-MS) has been used to define compositional end members in diagenetic and hydrothermal pyrite. The overgrowth of hydrothermal sulfides on diagenetic pyrite is associated with TE anomalism (Tl, Pb, As, Zn) that extends > 100 meters above the main high grade sulfide mineralization the Teena subbasin. The vertical zonation in TEs is consistent with the infiltration of hydrothermal fluids into overlying hangingwall sediments that were undergoing diagenesis. Bulk rock lithogeochemical data record covariation between total organic carbon (TOC) and a suite of TEs (Mo, Co, Ni, V). We suggest this was caused by local hydrographic factors during deposition of the Barney Creek Formation. High TOC/P molar ratios, resulting from regeneration of P in a euxinic water column, are associated with an interval overlying the main maximum flooding surface in the subbasin. The relationships between TOC, P and TEs resemble the redox architecture of a silled basin rather than an open marine margin. Sulfidic conditions developed during periods of high productivity, which were linked to nutrient supply that was enhanced by connectivity with surrounding water masses. The evidence of redox bistability, involving a delicate balance between ferruginous (anoxic, non-sulfidic) and euxinic (sulfidic) conditions, is consistent with recent models for other mid-Proterozoic sedimentary units. Nevertheless, there was a strong localised (101 km2) control on the authigenic and hydrothermal TE chemistry of the Barney Creek Formation in the Teena subbasin, which highlights a key challenge when extrapolating from data collected in partially restricted intracontinental marine settings

Pyrite chemistry records a multistage ore forming system at the Proterozoic George Fisher massive sulfide Zn-Pb-Ag deposit, Mount Isa, Australia

Trace element (TE) analysis of pyrite via LA-ICP-MS can be used to reconstruct the conditions of pyrite formation in complex mineral systems. The Carpentaria province in northern Australia is host to some of the world’s highest value Zn-Pb (+Ag, Cu) deposits. The genesis of many of these deposits is controversial, with competing models of single-vs. multi-stage ore formation. In this study, LA-ICP-MS data of paragenetically constrained pyrite from the George Fisher Zn-Pb-Ag deposit has been analysed to investigate the chemistry of different stages of ore formation. Pyrite from correlative unmineralized host rocks has also been analysed to investigate evidence of distal hydrothermal anomalism. All LA-ICP-MS data have been statistically evaluated (principal component analysis) and interpreted together with whole rock lithogeochemical data of the same samples. Pre-ore diagenetic pyrite is compositionally similar to other Proterozoic diagenetic pyrite, with some evidence of minor hydrothermal anomalism that with further analysis could help define distal alteration. Pyrite from the different ore stages are compositionally distinct, consistent with a multi-stage system. Ore stage 1 pyrite exceeds background contents of Co, Cu, Zn, As, Ag, Sb, Tl, and Pb and has elevated Co/Ni ratios, whereas only Ni and Co are above background abundances in ore stage 2 and 3 pyrite, of which only ore stage 3 pyrite has high Co/Ni ratios. Ore stage 1 pyrite has a similar composition to hydrothermal pyrite in the undeformed northern Carpentaria CD-type deposits and was likely syn-diagenesis. Ore stage 2 was syn-deformation, and resulted in replacement and recrystallization of pre-existing pyrite, and the expulsion of incompatible TEs. Ore stage 3 formed via a later Cu-Zn-Pb mineralizing event that resulted in a new geochemically distinct generation of Co-rich pyrite. Overall, this study demonstrates the value of paragenetically-constrained pyrite TE data for refining genetic models in complex sediment hosted mineral systems