Effect of genotype on individual response to the pharmacological treatment of glaucoma: a systematic review and meta-analysis

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. these drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. however, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. the present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated preferred reporting Items for systematic reviews and meta-analyses 2020 recommendations. the literature search was conducted consulting the most relevant scientific databases, i.e. pubmed/MEDLINE, scopus, web of science and public health genomics and precision health Knowledge base up to June 14th, 2023. the search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. the results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG. PROSPERO registration: CRD42023434867

Taxonomic resolution refinement does not improve understanding of invertebrate's role on leaf litter breakdown

Abstract The invertebrate biodiversity of subtropical streams depends on the seasonal input of organic matter, as much as the leaf decomposition process on stream system. However, one of the challenges in determining the importance of invertebrates for leaf breakdown in subtropical streams is the low taxonomic resolution applied in most studies. To overcome this limitation, here we used litter bags with senescent leaves to evaluate the impact of different taxonomic resolutions of trophic group classification to assess the seasonal importance of invertebrate community for leaf litter breakdown in a subtropical stream (Atlantic Forest in western of Paraná state, Brazil). Litterfall was quarterly measured over a year. The leaf litter accumulated in an interval of 30 days was retrieved, weighed, and used for the leaf breakdown experiments (by litter bags). We found a lower importance of invertebrate community richness and density (shredders and scrapers) in leaf breakdown process irrespective of the taxonomic resolution (family or genus level used). Hyphomycetes biomass and fungi sporulation also did not present changes among sample times, and consecutively, importance for leaf breakdown. However, the richness and density of Chironomidae taxa respond differently depending on the taxonomic resolution used. Low litter breakdown may be explained by the increase of consumption of microorganisms, due to high density of Chironomidae scrapers evaluated at the genus level. Moreover, temperature is the main factor responsible for breakdown over the year, in a positive way. Therefore, our results indicated the family level as the taxonomic resolution sufficient to assess the role of shredders and scrapers in the leaf litter breakdown process of this subtropical stream system

A New First Class Algebra, Homological Perturbation and Extension of Pure Spinor Formalism for Superstring

Based on a novel first class algebra, we develop an extension of the pure spinor (PS) formalism of Berkovits, in which the PS constraints are removed. By using the homological perturbation theory in an essential way, the BRST-like charge $Q$ of the conventional PS formalism is promoted to a bona fide nilpotent charge $\hat{Q}$, the cohomology of which is equivalent to the constrained cohomology of $Q$. This construction requires only a minimum number (five) of additional fermionic ghost-antighost pairs and the vertex operators for the massless modes of open string are obtained in a systematic way. Furthermore, we present a simple composite "$b$-ghost" field $B(z)$ which realizes the important relation $T(z) = \{\hat{Q}, B(z)\}$, with $T(z)$ the Virasoro operator, and apply it to facilitate the construction of the integrated vertex. The present formalism utilizes U(5) parametrization and the manifest Lorentz covariance is yet to be achieved.Comment: 38 pages, no figure. Proof of triviality of delta-homology improved and a reference adde

Superbrane Actions and Geometrical Approach

We review a generic structure of conventional (Nambu-Goto and Dirac-Born-Infeld-like) worldvolume actions for the superbranes and show how it is connected through a generalized action construction with a doubly supersymmetric geometrical approach to the description of super-p-brane dynamics as embedding world supersurfaces into target superspaces.Comment: Based on talks given by the authors at the Volkov Memorial Seminar "Supersymmetry and Quantum field Theory" (Kharkov, January 5-7, 1997), LaTeX file, 11 pages Misprints corrected, references adde

Evidence for the classical integrability of the complete AdS(4) x CP(3) superstring

We construct a zero-curvature Lax connection in a sub-sector of the superstring theory on AdS(4) x CP(3) which is not described by the OSp(6|4)/U(3) x SO(1,3) supercoset sigma-model. In this sub-sector worldsheet fermions associated to eight broken supersymmetries of the type IIA background are physical fields. As such, the prescription for the construction of the Lax connection based on the Z_4-automorphism of the isometry superalgebra OSp(6|4) does not do the job. So, to construct the Lax connection we have used an alternative method which nevertheless relies on the isometry of the target superspace and kappa-symmetry of the Green-Schwarz superstring.Comment: 1+26 pages; v2: minor typos corrected, acknowledgements adde

Generalized action principle and extrinsic geometry for N=1 superparticle

It is proposed the generalized action functional for N=1 superparticle in D=3,4,6 and 10 space-time dimensions. The superfield geometric approach equations describing superparticle motion in terms of extrinsic geometry of the worldline superspace are obtained on the base of the generalized action. The off-shell superdiffeomorphism invariance (in the rheonomic sense) of the superparticle generalized action is proved. It was demonstrated that the half of the fermionic and one bosonic (super)fields disappear from the generalized action in the analytical basis. Superparticle interaction with Abelian gauge theory is considered in the framework of this formulation. The geometric approach equations describing superparticle motion in Abelian background are obtained.Comment: 31 pages. Late

Lorentz harmonics and superfield action. D=10, N=1 superstring

We propose a new version of the superfield action for a closed D=10, N=1 superstring where the Lorentz harmonics are used as auxiliary superfields. The incorporation of Lorentz harmonics into the superfield action makes possible to obtain superfield constraints of the induced worldsheet supergravity as equations of motion. Moreover, it becomes evident that a so-called 'Wess-Zumino part' of the superfield action is basically a Lagrangian form of the generalized action principle. We propose to use the second Noether theorem to handle the essential terms in the transformation lows of hidden gauge symmetries, which remove dynamical degrees of freedom from the Lagrange multiplier superfield.Comment: 23 pages, latex, no figures. V.2, minor corrections, a reference adde

Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome

Mitochondrial mutations, an important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mitochondrial DNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally >70% of mutant mtDNA. We studied whether heteroplasmy level could be decreased by specifically designed oligoribonucleotides, targeted into mitochondria by the pathway delivering RNA molecules in vivo. Using mitochondrially imported RNAs as vectors, we demonstrated that oligoribonucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmitochondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases