Ofd1 Controls Dorso-Ventral Patterning and Axoneme Elongation during Embryonic Brain Development.

Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental disorder caused by mutations in the OFD1 gene. Similar to other inherited disorders associated to ciliary dysfunction OFD type I patients display neurological abnormalities. We characterized the neuronal phenotype that results from Ofd1 inactivation in early phases of mouse embryonic development and at post-natal stages. We determined that Ofd1 plays a crucial role in forebrain development, and in particular, in the control of dorso-ventral patterning and early corticogenesis. We observed abnormal activation of Sonic hedgehog (Shh), a major pathway modulating brain development. Ultrastructural studies demonstrated that early Ofd1 inactivation results in the absence of ciliary axonemes despite the presence of mature basal bodies that are correctly orientated and docked. Ofd1 inducible-mediated inactivation at birth does not affect ciliogenesis in the cortex, suggesting a developmental stage-dependent role for a basal body protein in ciliogenesis. Moreover, we showed defects in cytoskeletal organization and apical-basal polarity in Ofd1 mutant embryos, most likely due to lack of ciliary axonemes. Thus, the present study identifies Ofd1 as a developmental disease gene that is critical for forebrain development and ciliogenesis in embryonic life, and indicates that Ofd1 functions after docking and before elaboration of the axoneme in vivo

Effects of Cadmium Exposure on Gut Villi in Danio rerio.

In aquatic organisms, cadmium exposure occurs from ovum to death and the route of absorption is particularly wide, being represented by skin, gills and gastrointestinal tract, through which contaminated water and/or preys are ingested. It is known that cadmium interferes with the gut; however, less information is available on cadmium effects on an important component of the gut, namely goblet cells, specialized in mucus synthesis. In the present work, we studied the effects of two sublethal cadmium concentrations on the gut mucosa of Danio rerio. Particular attention was paid to changes in the distribution of glycan residues, and in metallothionein expression in intestinal cells. The results show that cadmium interferes with gut mucosa and goblet cells features. The effects are dose- and site-dependent, the anterior gut being more markedly affected than the midgut. Cadmium modifies the presence and/or distribution of glycans in the brush border and cytoplasm of enterocytes and in the goblet cells’ cytoplasm and alters the metallothionein expression and localization. The results suggest a significant interference of cadmium with mucosal efficiency, representing a health risk for the organism in direct contact with contamination and indirectly for the trophic chain

Women Ascending to Leadership Positions in Rural Nonprofit Organizations

This study investigates women’s experiences as they ascended to leadership roles in nonprofit organizations in rural communities, primarily in East Texas. The aim of this study is to understand the lived experiences of women in top management as they ascend into leadership positions, as the characteristics and experiences of effective leaders in rural nonprofits may differ from those of urban nonprofit agencies. There is limited research regarding women’s leadership experiences in rural nonprofit organizations. Using a phenomenological inquiry approach, we interviewed 32 women currently serving in leadership roles in rural nonprofit organizations. The research question guiding this phenomenological study was: What are female leaders’ lived experiences as they ascend to leadership positions? The interviews were audio recorded and professionally transcribed. Grounded theory approach was used to analyze the data. A total of 155 emergent themes were extracted by triangulation. After the major themes were extracted, 17 selective themes were identified based on leadership. The selective themes were condensed to three themes: 1) Leadership ascension, with six sub-themes of experience, micro-aggression, support, mentoring, training, and networking; 2) Leadership attributes; and 3) Leadership longevity. Despite the small number of participants, this in-depth study highlights the lived experiences of women leaders, providing a platform for further exploration into these experiences, especially in rural settings. Women in this study did not have an intentional leadership trajectory but rather were promoted within the organization. We found that gender impacts women’s leadership experiences. We also found that relational leadership styles in rural communities makes a difference for career longevity, and women consider honesty, compassion, integrity, self-awareness, and being a people person to be leadership attributes

Women Ascending to Leadership Positions in Rural Nonprofit Organizations

This study investigates women’s experiences as they ascended to leadership roles in nonprofit organizations in rural communities, primarily in East Texas. The aim of this study is to understand the lived experiences of women in top management as they ascend into leadership positions, as the characteristics and experiences of effective leaders in rural nonprofits may differ from those of urban nonprofit agencies. There is limited research regarding women’s leadership experiences in rural nonprofit organizations. Using a phenomenological inquiry approach, we interviewed 32 women currently serving in leadership roles in rural nonprofit organizations. The research question guiding this phenomenological study was: What are female leaders’ lived experiences as they ascend to leadership positions? The interviews were audio recorded and professionally transcribed. Grounded theory approach was used to analyze the data. A total of 155 emergent themes were extracted by triangulation. After the major themes were extracted, 17 selective themes were identified based on leadership. The selective themes were condensed to three themes: 1) Leadership ascension, with six sub-themes of experience, micro-aggression, support, mentoring, training, and networking; 2) Leadership attributes; and 3) Leadership longevity. Despite the small number of participants, this in-depth study highlights the lived experiences of women leaders, providing a platform for further exploration into these experiences, especially in rural settings. Women in this study did not have an intentional leadership trajectory but rather were promoted within the organization. We found that gender impacts women’s leadership experiences. We also found that relational leadership styles in rural communities makes a difference for career longevity, and women consider honesty, compassion, integrity, self-awareness, and being a people person to be leadership attributes

Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac–galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with ketogal did not produce significant variation in the expression of the two constitutive enzymes. Moreover, histological experiments on stomach and kidneys clearly indicated that repeated administration of ketogal induced lower toxicity than ketorolac. At same time, in vivo results clearly showed that both ketorolac and ketogal had a similar therapeutic activity in a model of inflammation and in pain perception. These effects were accompanied by the reduction of enzyme expression such as COX-2 and iNOS, and by the modulation of levels of nuclear NF-kB and cytosolic IkB-a in the inflamed paws. These very encouraging results demonstrate for the first time that ketogal could represent a valid and novel therapeutic alternative to the ketorolac and might pave the way for clinical studies

Antarctic climate, Southern Ocean circulation patterns, and deep water formation during the Eocene

We assess early-to-middle Eocene seawater neodymium (Nd) isotope records from seven Southern Ocean deep-sea drill sites to evaluate the role of Southern Ocean circulation in long-term Cenozoic climate change. Our study sites are strategically located on either side of the Tasman Gateway and are positioned at a range of shallow (Nd(t) = −9.3 ± 1.5). IODP Site U1356 off the coast of Adélie Land, a locus of modern-day Antarctic Bottom Water production, is identified as a site of persistent deep water formation from the early Eocene to the Oligocene. East of the Tasman Gateway an additional local source of intermediate/deep water formation is inferred at ODP Site 277 in the SW Pacific Ocean (εNd(t) = −8.7 ± 1.5). Antarctic-proximal shelf sites (ODP Site 1171 and Site U1356) reveal a pronounced erosional event between 49 and 48 Ma, manifested by ~2 εNd unit negative excursions in seawater chemistry toward the composition of bulk sediments at these sites. This erosional event coincides with the termination of peak global warmth following the Early Eocene Climatic Optimum and is associated with documented cooling across the study region and increased export of Antarctic deep waters, highlighting the complexity and importance of Southern Ocean circulation in the greenhouse climate of the Eocene

Insights from the Paleogene tropical Pacific: Foraminiferal stable isotope and elemental results from Site 1209, Shatsky Rise

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94995/1/palo1207.pd

Nejapa Tephra: The youngest (c. 1kaBP) highly explosive hydroclastic eruption in western Managua (Nicaragua)

Nejapa Maar (2.5 × 1.4 km, c. 120 m deep), the largest maar along the 15-km-long Holocene Nejapa–Miraflores Lineament (NML), is the source vent of the youngest relatively widespread basaltic tholeiitic tephra blanket (Nejapa Tephra: NT) in western central Nicaragua, as shown by isopachs and isopleths (Rausch and Schmincke, 2008). The NT covers an area of > 10 km2 in W/NW Managua. The minimum total magma volume erupted is estimated as 0.09 km3. Juvenile, dominantly slightly vesicular (20–40 vol.%) basically tachylitic cauliflower-shaped lapilli with an average density of 2.1 g/cm3, make up > 90 vol.% of the deposit, while lithoclasts comprise < 10 vol.% except proximally. This, the paucity of fine-grained tuffs and the dominant plane-parallel bedding all suggest fragmentation by shallow interaction of a rising magma starting to vesiculate and fragment pyroclastically with external water. The complex particles so generated erupted in moderately high eruption columns (at least 7–10 km) and were dominantly deposited as dry to damp, warm to cool fallout. Minor surge transport is inferred from fine-grained, locally cross-bedded tephra beds chiefly north of Nejapa and just west of Asososca Maars. Synvolcanic faulting along the NML is inferred. Faults in the study area indicate that activation of the N–S-trending Nejapa–Miraflores Fault (NMF), representing the western flank of Managua Graben, preceded deposition of NT and underlying Masaya Tuff (c.1.8 ka BP), Chiltepe Pumice (c. 1.9 ka BP) and Masaya Triple Layer (2.1 ka BP). The NT deposit is underlain regionally by a paleosol and topped by a soil. The basal paleosol contains pottery sherds made by the Usulután negative technique during the Late Formative period (700 BCE–300 CE) (2.7–1.7 ka BP). The soil overlying NT contains pottery related to the Ometepe technique dated as between 1350 and 1550 CE (650–450 a BP). These, and the radiocarbon dates of the pottery-bearing paleosols (1245 ± 125 and 535 ± 110 a BP) obtained by Pardo et al. (2008) indicate that Nejapa Maar erupted between c. 1.2 and 0.6 ka BP. Future eruptions in this area of similar magnitude, eruptive and transport mechanisms would represent a major hazard and risk to the densely populated western suburbs of Managua, a city expanding rapidly westward. Assuming a similar eruption scenario, poor-quality roofs, common in Nicaragua, would be prone to collapse up to 12 km peripheral to Nejapa Maar or another close-by eruptive site, and buildings at a distance of up to 500 m are likely to be severely affected. In view of the past frequency of eruptions along the NML, further eruptions are likely to occur in the near future

Developmental alterations in noxious-evoked EEG activity recorded from rat primary somatosensory cortex

Primary somatosensory cortex (S1) contains a nociceptive map that localizes potential tissue damage on the body and encodes stimulus intensity. An objective and specific biomarker of pain however is currently lacking and is urgently required for use in non-verbal clinical populations as well as in the validation of pre-clinical pain models. Here we describe studies to see if the responses of the S1 in juvenile rats are different to those in the adult. We recorded electroencephalogram (EEG) responses from S1 of lightly-anesthetized Sprague–Dawley rats at either postnatal day 21 or postnatal day 40 during the presentation of noxious (55 °C) or innocuous (30 °C) thermal stimuli applied to the plantar surface of the left hindpaw. The total EEG power across the recording period was the same in both ages after stimulation but the frequency distribution was significantly affected by age. Noxious heat evoked a significant increase in theta band (4–8 Hz) activity in adults only (P < 0.0001 compared to baseline; P < 0.0001 compared to juveniles). There were no significant differences in EEG responses to innocuous thermal stimuli. These data show that there are significant alterations in the processing of nociceptive inputs within the maturing cortex and that cortical theta activity is involved only in the adult cortical response to noxious stimulation

Reclaiming feminist futures : co-opted and progressive politics in a neoliberal age

This article engages with the influential narrative about the co-optation of feminism in conditions of neoliberalism put forward by prominent feminist thinkers Nancy Fraser, Hester Eisenstein and Angela McRobbie. After drawing out the twin visions of 'progressive' feminist politics that undergird this narrative — cached out in terms of either the retrieval of past socialist feminist glories or personal reinvention — we subject to critical scrutiny both the substantive claims made and the conceptual scaffolding invoked. We argue that the proleptic imaginings of all three authors, in different ways, are highly circumscribed in terms of the recommended agent, agenda and practices of progressive politics, and clouded by conceptual muddle over the meanings of 'left', 'radical' and 'progressive'. Taken together, these problems render the conclusions of Fraser, Eisenstein and McRobbie at best unconvincing and at worst dismissive of contemporary feminist efforts to challenge neoliberalism. We end the paper by disentangling and redefining left, radical and progressive and by sketching a contrasting substantive vision of progressive feminist politics enabled by this reconceptualisation