Future pain as present concern

Pain is multidimensional, complex; it affects the ontological structures of the human being and exceeds spatio-temporal boundaries. Therefore, it is universally felt with an impact in the past, moving to the present, and projecting to the future. There are efforts to ease or completely eliminate the impact of pain, however, a good understanding of its biological and anthropological dimensions is necessary for proper orientation of such undertakings. This article identifies some social, cultural, medical-scientific, and individual factors that account for the changes in modes of experiencing and managing pain. It posits that there is a general unpreparedness on the physical, psychological, and spiritual levels for continued pain in the future. It thus analyses factors that need to be learnt in order to promote favourable alterations in mental attitudes, pain sensitivity, and tolerance to pain. Preparing for a future of pain requires interdisciplinary reflection on the bodily, emotional, and spiritual components that constitute the pain experience so as to re-direct its trajectory.

Business Perception as a Strategy for Sustaining Entrepreneurship in the Face of Insurgency in Niger State, Nigeria

The Nigerian business environment is unfriendly considering the insecurity situation that characterized the atmosphere which resulted in many businesses being halted while others are forced to outright closure, especially in Niger state. As a result, government and policymakers in the state invest, support, and encourage entrepreneurs to sustain them. However, despite these huge investments and strategies adopted to promote and sustain entrepreneurship activities in the state by policymakers, entrepreneurs continued to perform below expectation. The study, therefore, examined perception as a strategy for sustainable entrepreneurship in the face of insurgency in Niger State. 315 respondents were used as the population as well as the sample size of the study. Simple linear regression was used to analyze the stated hypothesis. The study found a strong and positive relationship between business perception and entrepreneurship sustainability in Niger State. The study concludes that business perception is a strategy for sustainable entrepreneurship in Niger State and recommended that there should be proper orientation and encouragement to Niger State entrepreneurs to maintain or even improve on their current entrepreneurial mind- set, perceiving entrepreneurial opportunities amidst insecurity challenges.

Structural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis

Lipoproteins serve diverse functions in the bacterial cell and some are essential for survival. Some lipoproteins are adjuvants eliciting responses from the innate immune system of the host. The growing list of membrane enzymes responsible for lipoprotein synthesis includes the recently discovered lipoprotein intramolecular transacylase, Lit. Lit creates a lipoprotein that is less immunogenic, possibly enabling the bacteria to gain a foothold in the host by stealth. Here, we report the crystal structure of the Lit enzyme from Bacillus cereus and describe its mechanism of action. Lit consists of four transmembrane helices with an extracellular cap. Conserved residues map to the cap-membrane interface. They include two catalytic histidines that function to effect unimolecular transacylation. The reaction involves acyl transfer from the sn-2 position of the glyceryl moiety to the amino group on the N-terminal cysteine of the substrate via an 8-membered ring intermediate. Transacylation takes place in a confined aromatic residue-rich environment that likely evolved to bring distant moieties on the substrate into proximity and proper orientation for catalysis.

Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives

Over the past few decades, Ru catalyzed transfer hydrogenation (TH) and asymmetric transfer hydrogenation (ATH) reactions of unsaturated hydrocarbons, imine, nitro and carbonyl compounds have emerged as economic and powerful tools in organic synthesis. These reactions are most preferred processes having applications in the synthesis of fine chemicals to pharmaceuticals due to safe handling as these do not require hazardous pressurized H2 gas. The catalytic activity and selectivity of Ru complexes were investigated with a variety of ligands based on pincer NHC, cyclophane, half-sandwich, organophosphine etc. These ligands coordinate to Ru center in a proper orientation with a labile group replaced by H-source (like methanol, isopropanol, formic acid, dioxane, THF), which facilitate the β-hydrogen transfer to generate metal hydride species (Ru-H) and produce desired reduced product. This chapter describes the recent advances in TH and ATH reactions with homogeneous and heterogeneous Ru catalysts having different ligand environments and mechanistic details leading to their sustainable industrial applications.

Encoding and control of orientation to airflow by a set of Drosophila fan-shaped body neurons

The insect central complex (CX) is thought to underlie goal-oriented navigation but its functional organization is not fully understood. We recorded from genetically-identified CX cell types in Drosophila and presented directional visual, olfactory, and airflow cues known to elicit orienting behavior. We found that a group of neurons targeting the ventral fan-shaped body (ventral P-FNs) are robustly tuned for airflow direction. Ventral P-FNs did not generate a ‘map’ of airflow direction. Instead, cells in each hemisphere were tuned to 45° ipsilateral, forming a pair of orthogonal bases. Imaging experiments suggest that ventral P-FNs inherit their airflow tuning from neurons that provide input from the lateral accessory lobe (LAL) to the noduli (NO). Silencing ventral P-FNs prevented flies from selecting appropriate corrective turns following changes in airflow direction. Our results identify a group of CX neurons that robustly encode airflow direction and are required for proper orientation to this stimulus.

Proper Orientations of Chordal Graphs

An orientation D of a graph G = (V, E) is a digraph obtained from G by replacing each edge by exactly one of the two possible arcs with the same end vertices. For each v ∈ V(G), the indegree of v in D, denoted by dD−(v), is the number of arcs with head v in D. An orientation D of G is proper if dD−(u) ≠ dD−(v), for all uv ∈ E(G). An orientation with maximum indegree at most k is called a k-orientation. The proper orientation number of G, denoted by χ→(G), is the minimum integer k such that G admits a proper k-orientation. We prove that determining whether χ→(G) ≤ k is NP-complete for chordal graphs of bounded diameter. We also present a tight upper bound for χ→(G) on split graphs and a linear-time algorithm for quasi-threshold graphs.

PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA

ABSTRACTProper orientation of the mitotic spindle is critical for accurate development and morphogenesis. In human cells, spindle orientation is regulated by the evolutionarily conserved protein NuMA, which interacts with dynein and enriches it at the cell cortex. Pulling forces generated by cortical dynein orient the mitotic spindle. Cdk1-mediated phosphorylation of NuMA at threonine 2055 (T2055) negatively regulates its cortical localization. Thus, only NuMA not phosphorylated at T2055 localizes at the cell cortex. However, the identity and the mechanism of action of the phosphatase complex involved in T2055 dephosphorylation remains elusive. Here, we characterized the PPP2CA-B55γ (PPP2R2C)–PPP2R1B complex that counteracts Cdk1 to orchestrate cortical NuMA for proper spindle orientation. In vitro reconstitution experiments revealed that this complex is sufficient for T2055 dephosphorylation. Importantly, we identified polybasic residues in NuMA that are critical for T2055 dephosphorylation, and for maintaining appropriate cortical NuMA levels for accurate spindle elongation. Furthermore, we found that Cdk1-mediated phosphorylation and PP2A-B55γ-mediated dephosphorylation at T2055 are reversible events. Altogether, this study uncovers a novel mechanism by which Cdk1 and its counteracting PP2A-B55γ complex orchestrate spatiotemporal levels of cortical force generators for flawless mitosis.

CAMSAP3 facilitates basal body polarity and the formation of the central pair of microtubules in motile cilia

Synchronized beating of cilia on multiciliated cells (MCCs) generates a directional flow of mucus across epithelia. This motility requires a “9 + 2” microtubule (MT) configuration in axonemes and the unidirectional array of basal bodies of cilia on the MCCs. However, it is not fully understood what components are needed for central MT-pair assembly as they are not continuous with basal bodies in contrast to the nine outer MT doublets. In this study, we discovered that a homozygous knockdown mouse model for MT minus-end regulator calmodulin-regulated spectrin-associated protein 3 (CAMSAP3),Camsap3tm1a/tm1a, exhibited multiple phenotypes, some of which are typical of primary ciliary dyskinesia (PCD), a condition caused by motile cilia defects. Anatomical examination ofCamsap3tm1a/tm1amice revealed severe nasal airway blockage and abnormal ciliary morphologies in nasal MCCs. MCCs from different tissues exhibited defective synchronized beating and ineffective generation of directional flow likely underlying the PCD-like phenotypes. In normal mice, CAMSAP3 localized to the base of axonemes and at the basal bodies in MCCs. However, inCamsap3tm1a/tm1a, MCCs lacked CAMSAP3 at the ciliary base. Importantly, the central MT pairs were missing in the majority of cilia, and the polarity of the basal bodies was disorganized. These phenotypes were further confirmed in MCCs ofXenopusembryos when CAMSAP3 expression was knocked down by morpholino injection. Taken together, we identified CAMSAP3 as being important for the formation of central MT pairs, proper orientation of basal bodies, and synchronized beating of motile cilia.