The Role of Attractiveness in Gendered Sexual Response Patterns.

Previously documented sexual response patterns of gender-specificity among gynephilic men and gender-nonspecificity among gynephilic women could be explained by women responding more strongly to non-gendered aspects of sexual stimuli. Cues of attractiveness are known determinants of sexual decision-making, yet have not been directly tested as determinants of sexual response. The current study investigated the role of attractiveness cues in explaining gender-based patterns of sexual response.

AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.

Purpose: Complement dysregulation in the eye has been implicated in the pathogenesis of age-related macular degeneration (AMD), and genetic variants of complement factor H (CFH) are strongly associated with AMD risk. We therefore aimed to untangle the role of CFH and its splice variant, factor H-like 1 (FHL-1), in ocular complement regulation derived from local versus circulating sources. We assessed the therapeutic efficacy of adeno-associated viruses (AAVs) expressing human FHL-1 and a truncated version of CFH (tCFH), which retains the functional N- and C-terminal ends of the CFH protein, in restoring the alternative complement pathway in Cfh-/- mouse eyes and plasma.

Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease.

Neurodegenerative diseases (NDDs) are a heterogeneous group of diseases that are characterized by the progressive loss of neurons leading to motor, sensory, and/or cognitive defects. Currently, NDDs are not curable and treatment focuses on alleviating symptoms and halting disease progression. Phenotypic heterogeneity between individual NDD patients, lack of robust biomarkers, the limited translational potential of experimental models, and other factors have hampered drug development for the treatment of NDDs.

Dose Range Finding Studies with Two Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy.

Recombinant adeno-associated viral (rAAV) vector-mediated gene therapy is being developed to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator () gene. In preparation for a clinical gene therapy trial, we conducted dose range finding (DRF) studies with an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF) vector administered by subretinal injection in a naturally occurring -mutant canine model (XLPRA2) to compare two different human () transgenes and to establish a reasonable starting dose for a clinical trial. Different dose levels of two candidate vectors (0.

Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated rAAV2tYF-GRK1-, to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator () gene. The vector contains a codon-optimized human RPGR cDNA () driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1 [GRK1]), and is packaged in an AAV2 capsid variant with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a toxicity and efficacy study of this vector administered by subretinal injection in the naturally occurring mutant (X-linked progressive retinal atrophy 2 [XLPRA2]) dog model.

Ocular Inflammatory Response to Intravitreal Injection of Adeno-Associated Virus Vector: Relative Contribution of Genome and Capsid.

Both subretinal dosing and intravitreal (IVT) dosing of adeno-associated virus (AAV) in higher species induce mild and transient inflammatory responses that increase with dose. Foreign protein and foreign DNA are known inducers of inflammation, which is also true in the immune-privileged ocular environment. We explored which component(s) of AAV vectors, viral capsid, or viral DNA drive inflammatory responses.

A Case of Spontaneous Third Ventriculocisternostomy to the Interpeduncular Fossa.

Background: Triventricular hydrocephalus is caused by an obstruction of cerebrospinal fluid flow causing increased intracranial pressure (ICP). Common treatment options include ventricular shunting or endoscopic third ventriculocisternostomy. Spontaneous third ventriculocisternostomy is a rare phenomenon in patients with obstructive triventricular hydrocephalus.

Occurrence and mechanism of visual phosphenes in external photon beam radiation therapy and how to influence them.

Background And Purpose: Two plausible mechanisms to explain the appearance of visual phosphenes are: direct activation of the photochemicals in the retina and the generation of Cherenkov radiation in the vitreous humour. In this clinical trial we investigated the occurrence of visual phosphenes in external photon beam radiation therapy.

Material And Methods: Logistic regression analysis is used to examine whether seeing light flashes and seeing steady light depended on the ambient light intensity and the dose.

Alterations of root architecture and cell wall modifications in Tilia cordata Miller (Linden) growing on mining sludge.

Trees are considered good candidates for phytoremediation of soils contaminated with trace elements (TE), e.g. mine tailings.

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated AAV2tYF-GRK1-RPGRco, to treat retinitis pigmentosa (RP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The vector contains a codon-optimized human RPGR cDNA (RPGRco) driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1, GRK1) and is packaged in an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a safety and potency study of this vector administered by subretinal a injection in the naturally occurring RPGR-deficient Rd9 mouse model.

The Effects of Gender and Relationship Context Cues on Responsive Sexual Desire in Exclusively and Predominantly Androphilic Women and Gynephilic Men.

Sexual desire may be "responsive," emerging from sexual arousal to sexually competent cues. Cues that elicit sexual arousal and desire differ, however, by gender and direction of sexual attractions. Further, relationship context cues are thought to be important for responsive desire, but this has not been tested directly.

Gynephilic Men's Self-Reported and Genital Sexual Responses to Relationship Context Cues.

The current study examined men's sexual responses to relationship context. Chivers and Timmers (2012) previously reported that heterosexual men's genital and self-reported sexual arousal varied by gender but not relationship context, suggesting that gender cues are more salient determinants of sexual response than relationship context cues for men. Those analyses were, however, significantly underpowered to detect relationship context effects (n = 9).

LYR3, a high-affinity LCO-binding protein of Medicago truncatula, interacts with LYK3, a key symbiotic receptor.

LYR3, LYK3, and NFP are lysin motif-containing receptor-like kinases (LysM-RLKs) from Medicago truncatula, involved in perception of symbiotic lipo-chitooligosaccharide (LCO) signals. Here, we show that LYR3, a high-affinity LCO-binding protein, physically interacts with LYK3, a key player regulating symbiotic interactions. In vitro, LYR3 is phosphorylated by the active kinase domain of LYK3.

Light microscopy of whole plant organs.

Plants are ideal organisms for light microscopical studies of cellular mechanisms controlling cell organisation and cell functioning. However, most plant organs are not transparent to light which prevents high resolution imaging deep within plant tissues. Classically, access into plant organs is achieved by sectioning or whole-mount tissue clearing.

Molecular basis of lipo-chitooligosaccharide recognition by the lysin motif receptor-like kinase LYR3 in legumes.

LYR3 [LysM (lysin motif) receptor-like kinase 3] of Medicago truncatula is a high-affinity binding protein for symbiotic LCO (lipo-chitooligosaccharide) signals, produced by rhizobia bacteria and arbuscular mycorrhizal fungi. The present study shows that LYR3 from several other legumes, but not from two Lupinus species which are incapable of forming the mycorrhizal symbiosis, bind LCOs with high affinity and discriminate them from COs (chitooligosaccharides). The biodiversity of these proteins and the lack of binding to the Lupinus proteins were used to identify features required for high-affinity LCO binding.

Comparative analysis of the tubulin cytoskeleton organization in nodules of Medicago truncatula and Pisum sativum: bacterial release and bacteroid positioning correlate with characteristic microtubule rearrangements.

In this study we analyzed and compared the organization of the tubulin cytoskeleton in nodules of Medicago truncatula and Pisum sativum. We combined antibody labeling and green fluorescent protein tagging with laser confocal microscopy to observe microtubules (MTs) in nodules of both wild-type (WT) plants and symbiotic plant mutants blocked at different steps of nodule development. The 3D MT organization of each histological nodule zone in both M.

Straight but Not Narrow; Within-Gender Variation in the Gender-Specificity of Women's Sexual Response.

Gender differences in the specificity of sexual response have been a primary focus in sexual psychophysiology research, however, within-gender variability suggests sexual orientation moderates category-specific responding among women; only heterosexual women show gender-nonspecific genital responses to sexual stimuli depicting men and women. But heterosexually-identified or "straight" women are heterogeneous in their sexual attractions and include women who are exclusively androphilic (sexually attracted to men) and women who are predominantly androphilic with concurrent gynephilia (sexually attracted to women). It is therefore unclear if gender-nonspecific responding is found in both exclusively and predominantly androphilic women.

Auxin perception is required for arbuscule development in arbuscular mycorrhizal symbiosis.

Most land plant species live in symbiosis with arbuscular mycorrhizal fungi. These fungi differentiate essential functional structures called arbuscules in root cortical cells from which mineral nutrients are released to the plant. We investigated the role of microRNA393 (miR393), an miRNA that targets several auxin receptors, in arbuscular mycorrhizal root colonization.

Gender-specific genital and subjective sexual arousal to prepotent sexual features in heterosexual women and men.

Heterosexual women respond genitally to stimuli featuring both their preferred and nonpreferred genders, whereas men's genital responses are gender-specific, suggesting that gender cues are less relevant to women's sexual response. Instead, prepotent sexual features (exposed and sexually aroused genitals), ubiquitous in audiovisual sexual stimuli, may elicit automatic genital responses, thereby leading to a nonspecific sexual arousal pattern in women. To examine the role of stimulus potency in women's sexual response, we assessed heterosexual women's and men's genital and subjective sexual arousal to slideshows of prepotent stimuli (erect penises and aroused vulvas), non-prepotent stimuli (flaccid penises and female pubic triangles), and sexually neutral stimuli.

Effects of gender and relationship context in audio narratives on genital and subjective sexual response in heterosexual women and men.

Previous research suggests that heterosexual women's sexual arousal patterns are nonspecific; heterosexual women demonstrate genital arousal to both preferred and nonpreferred sexual stimuli. These patterns may, however, be related to the intense and impersonal nature of the audiovisual stimuli used. The current study investigated the gender specificity of heterosexual women's sexual arousal in response to less intense sexual stimuli, and also examined the role of relationship context on both women's and men's genital and subjective sexual responses.

A switch in Ca2+ spiking signature is concomitant with endosymbiotic microbe entry into cortical root cells of Medicago truncatula.

Ca(2+) spiking is a central component of a common signaling pathway that is activated in the host epidermis during initial recognition of endosymbiotic microbes. However, it is not known to what extent Ca(2+) signaling also plays a role during subsequent root colonization involving apoplastic transcellular infection. Live-tissue imaging using calcium cameleon reporters expressed in Medicago truncatula roots has revealed that distinct Ca(2+) oscillatory profiles correlate with specific stages of transcellular cortical infection by both rhizobia and arbuscular mycorrhizal fungi.

A nuclear-targeted cameleon demonstrates intranuclear Ca2+ spiking in Medicago truncatula root hairs in response to rhizobial nodulation factors.

Lipochitooligosaccharide nodulation factors (NFs) secreted by endosymbiotic nitrogen-fixing rhizobia trigger Ca(2+) spiking in the cytoplasmic perinuclear region of host legume root hairs. To determine whether NFs also elicit Ca(2+) responses within the plant cell nucleus we have made use of a nucleoplasmin-tagged cameleon (NupYC2.1).

Mechanism of infection thread elongation in root hairs of Medicago truncatula and dynamic interplay with associated rhizobial colonization.

In temperate legumes, endosymbiotic nitrogen-fixing rhizobia gain access to inner root tissues via a specialized transcellular apoplastic compartment known as the infection thread (IT). To study IT development in living root hairs, a protocol has been established for Medicago truncatula that allows confocal microscopic observations of the intracellular dynamics associated with IT growth. Fluorescent labeling of both the IT envelope (AtPIP2;1-green fluorescent protein) and the host endoplasmic reticulum (green fluorescent protein-HDEL) has revealed that IT growth is a fundamentally discontinuous process and that the variable rate of root hair invagination is reflected in changes in the host cell cytoarchitecture.

The role of the plant cytoskeleton in the interaction between legumes and rhizobia.

The study of the symbiotic interaction between rhizobia and legumes represents a major theme in plant biology. This interaction results in the formation of nodules, root organs in which the bacteria reduce atmospheric nitrogen into ammonia, which can subsequently be utilized by the plant. The execution of the different developmental stages observed during nodule ontogenesis involves many cellular processes with significant roles for the plant cytoskeleton.

Characterization of intraocular immunopathology following intracameral inoculation with alloantigen.

Purpose: Anterior chamber-associated immune deviation (ACAID) is a form of peripheral tolerance achieved via intracameral antigen inoculation. It is well known that ACAID effectively down-regulates potentially destructive immunities such as delayed-type hypersensitivity (DTH) at extraorbital sites. However, what has not been specifically addressed is whether local intraocular tissues are negatively affected from intracamerally placed antigen.