Prairie vole pups show potentiated isolation-induced vocalizations following isolation from their mother, but not their father.

Vocalizations can be markers of emotional social communication. Maternal potentiation was originally described as an increased rate of vocalization by isolated rat pups following an interaction with their mothers, but not with other social companions. Here we asked if potentiation in prairie voles, a species with pair-bonding and bi-parental rearing, is parent-specific. We found that isolated, 8-11-day-old voles exhibited potentiation following reunions with the dam, but not the sire. These responses were present whether parents were anesthetized or active during the reunion. There were no significant correlations between parental behaviors during reunions and pup vocalization rates during re-isolation. The absence of potentiation to the sire contrasts to findings in bi-parentally reared rat pups, which do potentiate vocalizations to the sire. We interpret these results to be consistent with the idea that potentiation reflects disruption of mother-infant coregulation and is dependent upon the unique biology of mothering. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:687-699, 2016.

World Trade Center Health Program: First Decade of Research.

The terrorist attacks on 11 September 2001 placed nearly a half million people at increased risk of adverse health. Health effects research began shortly after and continues today, now mostly as a coordinated effort under the federally mandated World Trade Center (WTC) Health Program (WTCHP). Established in 2011, the WTCHP provides medical monitoring and treatment of covered health conditions for responders and survivors and maintains a research program aimed to improve the care and well-being of the affected population. By 2020, funds in excess of USD 127 M had been awarded for health effects research. This review describes research findings and provides an overview of the WTCHP and its future directions. The literature was systematically searched for relevant articles published from 11 September 2001 through 30 June 2020. Synthesis was limited to broad categories of mental health, cancer, respiratory disease, vulnerable populations, and emerging conditions. In total, 944 WTC articles were published, including peer-reviewed articles funded by the WTCHP (n = 291) and other sources. Research has focused on characterizing the burden and etiology of WTC-related health conditions. As the program moves forward, translational research that directly enhances the care of individuals with chronic mental and physical health conditions is needed.

Microtubules in relation to the motility of a sperm syncytium in an armored scale insect.

Male scale insects of the species Parlatoria oleae Colvée (Homoptera: Coccoidea) produce motile sperm bundles. The bundle is a syncytium consisting of 10 to 20 closely packed, filamentous spermatozoa, which share a common cytoplasm and are enclosed in a common membrane. The individual spermatozoon is not surrounded by a plasma membrane, but is delimited by a scroll-like sheath composed of 45 to 50 microtubules. The microtubules run parallel to the long axis of the spermatozoon and are arranged in a spiral pattern as seen in transection. The outside diameter measures approximately 140 to 220 A and the inside diameter, 70 to 100 A. The spermatozoon is about 300 micro long and tapers gradually from a diameter of approximately 0.3 micro anteriorly to 0.1 micro posteriorly. The anterior half (150 micro) has a threadlike core of chromatin about 0.07 micro in diameter. A homogeneous cytoplasm surrounds the nuclear core and fills the posterior half of the spermatozoon. Neither osmium tetroxide nor glutaraldehyde fixation revealed the presence of a nuclear envelope, acrosomal membranes, mitochondria, flagellum, or centrioles. In spite of the apparent lack of orthodox cell organelles, the spermatozoon is actively motile upon release from the bundle. It exhibits capactiy for motility throughout its entire length. Since the sheath of microtubules is the only structure which extends the full length of the spermatozoon, it probably plays a significant role in spermatozoan motility.

Microtubular patterns in spermatozoa of coccid insects in relation to bending.

Flagella-like motion occurs in filamentous spermatozoa of coccid insects, which have diameters (0.16-0.65 micro) and lengths (150-300 micro) similar to those of long flagella, but have no doublets or 9 + 2-like arrangements of microtubules. Light and electron microscope investigations of spermatozoa from 10 species reveal many bizarre patterns of microtubules and suggest some basic similarities to flagella. Detailed analyses of spermatozoa which are naturally bent in definable planes during their elongation in the male and their storage in the female provide evidence that a constant topographical relationship is maintained between their unorthodox patterns of microtubules, as viewed in transections, and the direction of bending. The configuration common to most coccid spermatozoa consists of an acentrically positioned crescent of microtubules surrounded by one to several concentric rings. A line drawn to connect the two ends of the crescent appears to remain perpendicular to the plane of bending, and it defines a plane in which bisection of the spermatozoon produces halves with unequal numbers of microtubules. Bisection of the 9 + 2 motile apparatus in a plane perpendicular to that of bending also appears to produce halves with unequal numbers of microtubules. Therefore, the indispensable elements for flagellar and flagella-like motion may be microtubules arranged in "asymmetric" patterns.

Unusual microtubular patterns and three-dimensional movement of mealybug sperm and sperm bundles.

The spermatozoon of the mealybug Pseudococcus obscurus Essig is a filamentous cell (0.25 micro by 300 micro) which exhibits three-dimensional flagellations throughout most of its length. It has microtubules (200 A diameter) and a threadlike nuclear core (0.07-0.09 micro diameter) which extend almost its entire length, but apparently it has no mitochondria, centrioles, typical flagellum, or acrosome. The microtubules are arranged in two and a half concentric rings and total 56 in the most actively motile region but form two or three concentric rings with totals of 28 or 56 tubules, respectively, in less active regions. The relation of unusual microtubular patterns to the 9 + 2 complex and to flagellar motion is discussed. Mealybug spermatozoa are transmitted to the female in motile bundles which are approximately 1.3 micro by 750 micro and have four regions: (1) an anterior corkscrew region; (2) a region which contains approximately 16 spermatozoa; (3) a region of amorphous content; and (4) an endpiece. Bundle motility originates from the synchronous movements of its spermatozoa which appear to be arranged in two concentric multistranded helices. The spermatozoa provide both forward and gyratory motions of the bundle, and the corkscrew complements bundle propulsion by converting part of the rotation into forward movement.

Determination of iodine concentration and distribution in rat thyroid follicles by electron-probe microanalysis.

The concentration and the distribution of iodine in various sized follicles of rat thyroid glands have been analyzed by electron-probe microanalysis. The results of the iodine analysis were grouped according to uncorrected lumen diameter size. No significant differences in iodine concentration were observed among the various size categories. When the results for all follicles from a given sample were pooled, the standard error of the mean was approximately 4%. Usually 40-50 follicles per animal were analyzed. The concentration of iodine ranged from 0.9 to 2.1% by weight among individual animals. Scanning pictures and step-scan analysis showed the iodine distribution to be quite uniform across the colloid area. Several techniques of sample preparation were used; they produced no significant differences in the iodine concentrations observed. Sodium concentration, also determined in all samples, was found to vary from 2 to 9% by weight. Because of the mobility of the sodium ion, its distribution was greatly affected by the method of sample preparation. The technique that best preserved the natural chemistry of the sample was that of freezing the tissue, sectioning, and then freeze-drying.

Effects of cyclic AMP and Sephadex fractions of chick embryo extract on cloned retinal pigmented epithelium in tissue culture.

The effects of dibutyryl cyclic 3',5'-adenosine monophosphate (BcAMP) and Sephadex G-25 fractions of chick embryo extract on the growth rate, morphology, and pigmentation of normal chick retinal pigmented epithelium (PE) were investigated. Seven cloned PE cell lines were each grown in modified Ham's F-12 medium alone (F-12), or in F-12 supplemented with either high molecular weight (H) or low molecular weight (L) fractions of chick embryo extract. Cells grown in F-12 alone or in L medium formed compact epithelial sheets, whereas cells grown in H had a fibrocytic appearance and formed poorly organized monolayers. In H plus BcAMP, cell morphology was more epithelioid than in H alone, and generally the monolayers appeared more differentiated. Under each of these three culture conditions, 2 x 10(-4) M BCAMP retarded the increase in cell number and decreased the final number of cells per culture dish, but had little effect on plating efficiency. BcAMP also increased the rate of cell adhesion to a plastic substratum. Pigmentation was marked in cultures grown in F-12 or in L alone, but the addition of BcAMP dramatically reduced visible pigmentation. This effect was reversed when BcAMP was removed from the culture medium. Thus BcAMP modifies cell and colonial morphology, rate of cell accumulation, adhesive properties, and pigmentation of normal PE cells.

Retinal capillaries: proliferation of mural cells in vitro.

Capillaries from bovine, monkey, and human retinas maintained in tissue culture produced a monolayer of cells. Autoradiographic and electron microscopic evidence indicated that the mural cells (intramural pericytes) were the cells that proliferated. Since intramural pericytes are damaged selectively in diabetes mellitus, their availability in culture will be useful in seeking means to control diabetic retinopathy.

Retinal capillaries: basement membrane thickening by galactosemia prevented with aldose reductase inhibitor.

A twofold thickening of capillary basement membranes of rat retinas resulting from dietary galactose was prevented by sorbinil, an inhibitor of aldose reductase. Since the basement membrane thickening was ultrastructurally similar to that typical of diabetic retinopathy, it may indicate changes in vessel permeability and susceptibility to hemorrhage. Galactosemic rats should be useful models for studying basement membrane-related complications of diabetes and for examining the potential biochemical regulation of basement membrane synthesis by aldose reductase inhibitors.

Can teenage novel users perform as well as General Surgery residents upon initial exposure to a robotic surgical system simulator?

New techniques in minimally invasive and robotic surgical platforms require staged curricula to insure proficiency. Scant literature exists as to how much simulation should play a role in training those who have skills in advanced surgical technology. The abilities of novel users may help discriminate if surgically experienced users should start at a higher simulation level or if the tasks are too rudimentary. The study's purpose is to explore the ability of General Surgery residents to gain proficiency on the dVSS as compared to novel users. The hypothesis is that Surgery residents will have increased proficiency in skills acquisition as compared to naive users. Six General Surgery residents at a single institution were compared with six teenagers using metrics measured by the dVSS. Participants were given two 1-h sessions to achieve an MScoreTM in the 90th percentile on each of the five simulations. MScoreTM software compiles a variety of metrics including total time, number of attempts, and high score. Statistical analysis was run using Student's t test. Significance was set at p value <0.05. Total time, attempts, and high score were compared between the two groups. The General Surgery residents took significantly less Total Time to complete Pegboard 1 (PB1) (p = 0.043). No significant difference was evident between the two groups in the other four simulations across the same MScoreTM metrics. A focused look at the energy dissection task revealed that overall score might not be discriminant enough. Our findings indicate that prior medical knowledge or surgical experience does not significantly impact one's ability to acquire new skills on the dVSS. It is recommended that residency-training programs begin to include exposure to robotic technology.

Harnessing mHealth technologies to increase physical activity and prevent cardiovascular disease.

Research into prevention of cardiovascular disease has increasingly focused on mobile health (mHealth) technologies and their efficacy in helping individuals adhere to heart-healthy recommendations, including daily physical activity levels. By including the use of mHealth technologies in the discussion of physical activity recommendations, clinicians empower patients to play an active daily role in modifying their cardiovascular risk-factor profile. In this review, we critically evaluate the mHealth and physical activity literature to determine how these tools may lower cardiovascular risk while providing real-time tracking, feedback, and motivation on physical activity levels. We analyze the various domains-including user knowledge, social support, behavioral change theory, and self-motivation-that potentially influence the effectiveness of smartphone applications to impact individual physical activity levels. In doing so, we hope to provide a thorough overview of the mHealth landscape, in addition to highlighting many of the administrative, reimbursement, and patient-privacy challenges of using these technologies in patient care. Finally, we propose a behavioral change model and checklist for clinicians to assist patients in utilizing mHealth technology to best achieve meaningful changes in daily physical activity levels.

Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient mice.

We have constructed an ALDH3a1 null mouse to investigate the role of this enzyme that comprises nearly one-half of the total water-soluble protein in the mouse corneal epithelium. ALDH3a1-deficient mice are viable and fertile, have a corneal epithelium with a water-soluble protein content approximately half that of wild-type mice, and contain no ALDH3a1 as determined by zymograms and immunoblots. Despite the loss of protein content and ALDH3a1 activity, the ALDH3a1(-/-) mouse corneas appear indistinguishable from wild-type corneas when examined by histological analysis and electron microscopy and are transparent as determined by light and slit lamp microscopy. There is no evidence for a compensating protein or enzyme. Even though the function of ALDH3a1 in the mouse cornea remains unknown, our data indicate that its enzymatic activity is unnecessary for corneal clarity and maintenance, at least under laboratory conditions.

Peptidyl-puromycin synthesis by free and membrane-bound ribosomes.

The peptidyl transferase reaction, as measured by the formation of peptidyl-puromycin, was compared for free ribosomes and ribosomes bound to two types of membrane, the endoplasmic reticulum and the outer nuclear membrane. In most respects the reaction catalyzed by the three types of ribosome was similar, demonstrating that interaction of the 60 S ribosomal subunit with the membrane has little effect on the functioning of peptidyl transferase, a 60 S protein. However, both the rate and extent of synthesis of peptidyl puromycin were lower for ribosomes bound to the nuclear membrane than for free or microsome-bound ribosomes. This difference appears to be a direct consequence of the ribosome-membrane interaction, since ribosomes stripped from the nuclear membrane could not be distinguished from the other classes of ribosome.

Dietary vitamins A and E influence retinyl ester composition and content of the retinal pigment epithelium.

Experiments were conducted to determine the influence of dietary levels of vitamin A and alpha-tocopherol on the amounts and composition of retinyl esters in the retinal pigment epithelium of light-adapted albino rats. Groups of rats were fed diets containing alpha-tocopherol and either no retinyl palmitate, adequate retinyl palmitate, or excessive retinyl palmitate. Other groups of rats received diets lacking alpha-tocopherol and containing the same three levels of retinyl palmitate. Retinoic acid was added to diets lacking retinyl palmitate. After 27 weeks, the animals were light-adapted to achieve essentially total visual pigment bleaches, and the neural retinas and retinal pigment epithelium-eyecups were then dissected from each eye for vitamin A ester determinations. Almost all of the retinyl esters were found in the retinal pigment epithelium-eyecup portions of the eyes, mainly as retinyl palmitate and retinyl stearate. Maintaining rats on a vitamin A-deficient, retinoic acid-containing diet led to significant reductions in retinal pigment epithelial retinyl ester levels in rats fed both the vitamin E-supplemented and vitamin E-deficient diets; contrary to expectations, the effect of dietary vitamin A deficiency was more pronounced in the vitamin E-supplemented rats. Vitamin A deficiency in retinoic acid-maintained animals also led to significant reductions in retinyl palmitate-to-stearate ester ratios in the retinal pigment epithelia of both vitamin E-supplemented and vitamin E-deficient rats. Excessive dietary intake of vitamin A had little, if any, effect on retinal pigment epithelial retinyl ester content or composition. Vitamin E deficiency resulted in significant increases in retinal pigment epithelial retinyl palmitate content and in palmitate-to-stearate ester ratios in rats fed all three levels of vitamin A, but had little effect on retinal pigment epithelial retinyl stearate content. In other tissues, vitamin E deficiency has been shown to lower vitamin A levels, and it is widely accepted that this effect is due to autoxidative destruction of vitamin A. The increase in retinal pigment epithelial vitamin A ester levels in response to vitamin E deficiency indicates that vitamin E does not regulate vitamin A levels in this tissue primarily by acting as an antioxidant, but rather may act as an inhibitor of vitamin A uptake and/or storage. The effect of vitamin E on pigment epithelial vitamin A levels may be mediated by the vitamin E-induced change in retinyl palmitate-to-stearate ratios.

Prevention of basement membrane thickening in retinal capillaries by a novel inhibitor of aldose reductase, tolrestat.

A diabetic-like thickening of retinal capillary basement membranes induced in rats fed for 207 consecutive days a diet containing 50% galactose was prevented by the addition to the diet of tolrestat, a potent, structurally novel inhibitor of aldose reductase. Analysis of electron micrographs (X 25,000) of capillaries from the outer plexiform layer of the retina by computer planimetry showed that the basement membranes were approximately twofold thicker in rats fed galactose than in those fed either a standard diet or a diet containing galactose and tolrestat in doses of 43 or 57 mg/kg/day. The thickening of basement membranes in galactose-fed rats was accompanied by other ultrastructural alterations mimicking changes typical of diabetic microangiopathy, such as multilamination and the formation of vacuoles and dense inclusions. Therefore, the galactosemic rat represents a useful model for studying basement membrane-related complications of diabetes and their possible prevention by aldose reductase inhibitors.

Transscleral-RPE permeability of PEDF and ovalbumin proteins: implications for subconjunctival protein delivery.

PURPOSE: To investigate the in vitro, ex vivo, and in vivo transscleral-retinal pigment epithelium (RPE) permeability of PEDF and structurally related proteins for the exploration of novel routes of protein delivery to the retina. METHODS: Monkey RPE cells were cultured on permeable supports to separate apical and basal compartments. Porcine scleral tissue was placed in Ussing chambers to separate uveal and orbital compartments. Transepithelial resistance and voltage were measured by an electrical resistance system, and paracellular tracer flux was evaluated with trypan blue. Subconjunctival administration in rat eyes was by injections of soluble protein or by implantation of polyvinyl alcohol devices containing protein. Fluorescein-conjugated (Fl-) PEDF and ovalbumin were determined by spectrofluorometry, laser scanning, immunoblotting, epifluorescence, and confocal microscopy. Permeability was assessed by fluoresceinated-protein flux. RESULTS: Transepithelial resistance, impermeability to trypan blue, and confocal microscopy confirmed functional and structural tight junction formation of RPE cells cultured on permeable supports. Full-length Fl-PEDF and Fl-ovalbumin proteins diffused through RPE cell monolayers from either the apical or basal side. Fl-ovalbumin diffused through scleral tissues at constant rates. Subconjunctival Fl-PEDF or Fl-ovalbumin administration in vivo revealed movement of full-length protein into the choroid and retina as early as 1 hour. CONCLUSIONS: The sclera and RPE were permeable in vitro, ex vivo, and in vivo to PEDF and ovalbumin proteins. These large proteins can traverse through the sclera-RPE to reach the retina. In addition, these data prompt the proposal that subconjunctival protein delivery may represent a feasible and minimally invasive route for PEDF administration in the clinic.

Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the "four-eyed" fish (Anableps anableps).

The water meniscus bisects the eyes of the "four-eyed" fish Anableps anableps, resulting in simultaneous vision in air and water. We compare the structure and macromolecular compositions of the Anableps dorsal (air) and ventral (water) corneas with the fully aquatic zebrafish cornea. The Anableps dorsal corneal epithelium is thicker (>20 cell layers), flatter (approximately 1.94 mm radius of curvature), and contains approximately 15-fold more glycogen (0.16 microg/microg water-soluble protein) than the ventral corneal epithelium (5-7 cell layers; approximately 1.63 mm radius of curvature; 0.01 microg glycogen/microg water-soluble protein), which resembles the zebrafish corneal epithelium. Gelsolin is the major water-soluble protein in the zebrafish (approximately 50%) and Anableps dorsal (approximately 38%) and ventral (approximately 21%) corneal epithelia, suggesting that gelsolin was recruited for high corneal expression before these two species diverged at least 100 million years ago and that abundant corneal gelsolin is not limited to aquatic vision. Anableps gelsolin, deduced from its cDNA, is 57% identical to zebrafish gelsolin. Paucity of Anableps corneal F-actin (consistent with high gelsolin) was confirmed by the absence of rhodamine-phalloidin staining. We suggest amphibious refraction and protection from UV irradiation and desiccation in air as selective constraints for the specializations of the Anableps dorsal cornea.

Senescence and the retinal pigment epithelium: alterations in basal plasma membrane morphology.

Marked age-related changes in the morphology of retinal pigment epithelial (RPE) cell basal infoldings were found in pigmented rats. Quantitative morphometric analysis revealed that during senescence the amount of basal plasma membrane per unit RPE length increased substantially, the regional distribution of the basal infoldings along the RPE became more irregular, and the average depth of penetration of the basal infoldings into the RPE increased dramatically. The crucial role of the RPE in maintaining retinal integrity suggests that the observed changes in RPE morphology may be involved in the development of senile retinopathies which occur in a variety of species, including man.

Lipofuscin autofluorescence: evidence for vitamin A involvement in the retina.

A lipofuscin-like autofluorescence develops in the degenerating photoreceptor cells of the RCS rat, a strain with inherited retinal dystrophy. In animals with normal retinas, age-related lipofuscin accumulation in the eye is restricted to the retinal pigment epithelium (RPE). Previous investigations have established that RPE lipofuscin accumulation in the normal rat retina can be reduced by dietary vitamin A deficiency. In order to determine whether the photoreceptor-derived fluorescence in the RCS rat retina is related to RPE lipofuscin fluorescence, the influence of dietary vitamin A on the fluorophore content of the RCS rat retina was studied. Vitamin A deficiency substantially reduced the autofluorescence associated with degenerating photoreceptor cells of the RCS rat retina. A specific vitamin A-dependent fluorophore was isolated from these retinas using thin-layer chromatography (TLC). The mobility of this fluorophore on TLC differs from that of the major age-dependent fluorophore isolated from the RPE of normal rats. Thus, if the vitamin A-dependent fluorophores of the photoreceptors and RPE are related, it appears that the fluorophore generated in the photoreceptor cells must undergo chemical modification once it has been taken up by the RPE. The fact that both the RPE- and photoreceptor-associated fluorophores are vitamin A-dependent suggests that such a relationship between them is likely. These experiments indicate that the RPE is somewhat different from other lipofuscin-accumulating tissues in that a major precursor of RPE lipofuscin fluorophores originates in another cell type and enters the RPE via phagocytosis.

Relationship between dietary retinol and lipofuscin in the retinal pigment epithelium.

A variety of evidence suggests that autoxidation of cellular components probably plays a significant role in the age-related accumulation of lipofuscin, or age-pigment, in the mammalian retinal pigment epithelium (RPE). Among the likely candidates for conversion into RPE lipofuscin fluorophores via autoxidative mechanisms are vitamin A compounds, which are present in the retina and RPE in high concentrations. Vitamin E, an important lipid antioxidant, is likely to inhibit vitamin A autoxidation. Experiments were conducted to evaluate the significance of vitamin A autoxidation in the deposition of lipofuscin in the RPE. Albino rats were fed diets either supplemented with or lacking vitamin E. Each of these two groups of animals was further subdivided into three groups which were fed different levels of vitamin A palmitate: none, 14.0 mumol/kg diet, and 80.5 mumol/kg diet. After 26 weeks, the animals were killed and the RPE lipofuscin contents were determined by both fluorescence measurements and quantitative ultrastructural morphometry. Vitamin A palmitate deficiency led to significant reductions in RPE lipofuscin deposition, relative to the amounts of this pigment present in the groups receiving vitamin A palmitate in their diets. The relative magnitude of the vitamin A effect was greater in the vitamin E-supplemented groups than in the groups fed the diets deficient in vitamin E. This finding suggests that vitamin E interacts with vitamin A ester metabolites in vivo in a more complex manner than simply acting as an antioxidant protectant. Rats fed the diets containing the higher level of vitamin A palmitate failed to display elevated RPE lipofuscin contents relative to those in the rats fed 14.0 mumol of vitamin A palmitate/kg diet. Failure of high vitamin A intake to enhance RPE lipofuscin deposition may have been due to the fact that intake of vitamin A above normal levels did not lead to an elevation in vitamin A content of the retinal tissue. Establishing an effect of vitamin A deficiency on RPE lipofuscin deposition and characterization of the interactions between vitamins E and A are important steps toward defining precisely the molecular and cellular mechanisms underlying age-pigment accumulation in the RPE.