Cyclin D(1) expression during rat mammary tumor development and its potential role in the resistance of the Copenhagen rat

BACKGROUND: Resistance to mammary tumorigenesis in Copenhagen rats is associated with loss of early preneoplastic lesions known as intraductal proliferations. The cause of this disappearance, however, is unknown. RESULTS: There were no differences in the numbers of lesions in mammary whole-mounts prepared from Copenhagen or Wistar-Furth rats at 20 or 30 days after N-methyl-N-nitrosourea treatment, but at 37 days there were significantly fewer lesions in Copenhagen glands. Furthermore, lesions in Copenhagen glands were exclusively intraductal proliferations, whereas in Wistar-Furth glands more advanced lesions were also present. Immunohistochemical staining showed frequent cyclin D(1) overexpression in Wistar-Furth lesions at 37 days, but not in Copenhagen lesions. There were, however, no differences in p16(INK4a) protein expression, bromodeoxyuridine labeling and apoptotic indices, or mast cell infiltration between Copenhagen and Wistar-Furth lesions at any time. CONCLUSIONS: Overexpression of cyclin D(1) in preneoplastic lesions may be important in the development of mammary tumors in susceptible rats, although this overexpression does not appear to cause significant changes in cell kinetics. Furthermore, the low levels of cyclin D(1) expression in Copenhagen intraductal proliferations may play a role in the resistance of these rats to mammary tumorigenesis

Increased risk of depression in non-depressed HIV infected men with sleep disturbance: Prospective findings from the Multicenter AIDS Cohort Study.

ObjectiveSleep disturbance is a known risk factor for depression, but it is not known whether sleep disturbance contributes to greater risk of depression in those infected with human immunodeficiency virus (HIV+) as compared to those uninfected with HIV (HIV-).MethodsUsing data from the Multicenter AIDS Cohort Study, a population-based prospective study of men who have sex with men (MSM), self-reported sleep disturbance (>2 weeks) and depressive symptoms (Clinical Epidemiologic Scale for Depression, CES-D) were assessed every 6 months over 12 years of follow-up. Adjusted mixed effects logistic regression analyses tested whether sleep disturbance predicted depression (CES-D ≥ 16) at the immediate subsequent visit, and so on over 12 years, in non-depressed HIV+(N = 1054; 9556 person-visits) and non-depressed HIV- (N = 1217; 12,680 person-visits). In HIV+ vs. HIV- MSM, linearly estimated average incidence of depression and normalized cumulative rate of depression over 12 years were compared.ResultsIn the HIV+ MSM, sleep disturbance was associated with a significant increase in depression 6 months later (OR = 1.6; 95% CI, 1.30, 1.96), which was significantly greater (P < .05) than in HIV- MSM (OR = 1.16; 95% CI, 0.94, 1.44). HIV status and sleep disturbance interacted (P < .001), such that incidence of depression and normalized cumulative rate of depression were greater in HIV+ with sleep disturbance than in HIV+ without sleep disturbance and HIV- groups (all P's < 0.001).ConclusionsHIV+ persons who report sleep disturbance represent a high risk group to be monitored for depression, and possibly targeted for insomnia treatment to prevent depression. FUND: National Institute of Allergy and Infectious Diseases

Fish community response to in-channel woody debris in a channelized river system

Additions of large wood (LW) have become a go-to technique for recovering altered river ecosystems. However, successful applications of this technique are generally limited to unchannelized rivers and headwater streams. Channelization of rivers, that is, engineering river channels to reduce recruitment and retention of in-channel structure, may, by definition, limit success of this restoration technique. Moreover, sufficient time has passed (a century or more) since initial channelization of many large rivers that portions of the fish community associated with LW may have become extirpated. Thus, the maxim that LW leads to a positive fish community response may not hold true. We examined fish community associations in habitats with and without LW in the channelized Missouri River to gain an understanding of the role of LW in large, channelized rivers. There were some differences between habitats with wood present compared to those without, but the differences were not evident once year, season and channel modifications intended to create aquatic habitat were taken into account. We assert that careful planning is necessary to ensure that additions of LW in channelized rivers are made to appropriate locations such that it will be retained in-channel for use as fish habitat and that LW-associated species are found in the system

Properties of magnetohydrodynamic normal modes in the Earth’s magnetosphere

Funding: MDH was supported by NASA 80NSSC19K0127, 80NSSC19K0907, 80NSSC21K1683, 80NSSC21K1677, 80NSSC23K0903, and NSF AGS-2307204. KT was supported by NASA 80NSSC19K0259 and 80NSSC21K0453. MOA was supported by a UKRI (STFC / EPSRC) Stephen Hawking Fellowship EP/T01735X/1. The research of A.W. was funded in part by Science and Technology Facilities Council (STFC) grant ST/W001195/1 (UK). T.E. was funded in part by a Leverhulme Early Career Fellowship ECF-2019-155 (UK). AA and XZ were supported by NASA 80NSSC21K0729 and 80NSSC23K0108. We acknowledge support from ISSI Bern through ISSI International Team projects 483 “The Identification And Classification Of 3D Alfven Resonances” and 546 “Magnetohydrodynamic Surface Waves at Earth’s Magnetosphere (and Beyond).” We acknowledge NASA contract NAS5-02099.The Earth's magnetosphere supports a variety of Magnetohydrodynamic (MHD) normal modes with Ultra Low Frequencies (ULF) including standing Alfvén waves and cavity/waveguide modes. Their amplitudes and frequencies depend in part on the properties of the magnetosphere (size of cavity, wave speed distribution). In this work, we use ∼13 years of Time History of Events and Macroscale Interactions during Substorms satellite magnetic field observations, combined with linearized MHD numerical simulations, to examine the properties of MHD normal modes in the region L > 5 and for frequencies 5 depend on both the magnetopause location and the location of peaks in the radial Alfvén speed profile. Finally, we discuss how these results might be used to better model radiation belt electron dynamics related to ULF waves.PostprintPeer reviewe

Dose-finding study of a 90-day contraceptive vaginal ring releasing estradiol and segesterone acetate.

ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200 mcg/day and segesterone acetate (SA) 200 mcg/day to identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40 pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n = 22), 100 (n = 21), and 200 (n = 22) mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100 mcg/day groups were <40 pg/mL. In the 200 mcg/day group, median E2 concentrations peaked on days 4-5 of CVR use at 194 pg/mL (range 114-312 pg/mL) and remained >40 pg/mL throughout 30 days; E2 concentrations were 37 pg/mL (range 28-62 pg/mL) on days 88-90 (n = 11). Among the E2 200 mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200 mcg/day and SA 200 mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200 mcg/day and segesterone acetate 200 mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation

A context-dependent switch from sensing to feeling in the primate amygdala

The skin transmits affective signals that integrate into our social vocabulary. As the socio-affective aspects of touch are likely processed in the amygdala, we compare neural responses to social grooming and gentle airflow recorded from the amygdala and the primary somatosensory cortex of non-human primates. Neurons in the somatosensory cortex respond to both types of tactile stimuli. In the amygdala, however, neurons do not respond to individual grooming sweeps even though grooming elicits autonomic states indicative of positive affect. Instead, many show changes in baseline firing rates that persist throughout the grooming bout. Such baseline fluctuations are attributed to social context because the presence of the groomer alone can account for the observed changes in baseline activity. It appears, therefore, that during grooming, the amygdala stops responding to external inputs on a short timescale but remains responsive to social context (or the associated affective states) on longer time scales

Management of Intracranial Meningiomas Using Keyhole Techniques

BACKGROUND: Keyhole craniotomies are increasingly being used for lesions of the skull base. Here we review our recent experience with these approaches for resection of intracranial meningiomas. METHODS: Clinical and operative data were gathered on all patients treated with keyhole approaches by the senior author from January 2012 to June 2013. Thirty-one meningiomas were resected in 27 patients, including 9 supratentorial, 5 anterior fossa, 7 middle fossa, 6 posterior fossa, and 4 complex skull base tumors. Twenty-nine tumors were WHO Grade I, and 2 were Grade II. RESULTS: The mean operative time was 8 hours, 22 minutes (range, 2:55-16:14) for skull-base tumors, and 4 hours, 27 minutes (range, 1:45-7:13) for supratentorial tumors. Simpson Resection grades were as follows: Grade I = 8, II = 8, III = 1, IV = 15, V = 0. The median postoperative hospital stay was 4 days (range, 1-20 days). In the 9 patients presenting with some degree of visual loss, 7 saw improvement or complete resolution. In the 6 patients presenting with cranial nerve palsies, 4 experienced improvement or resolution of the deficit postoperatively. Four patients experienced new neurologic deficits, all of which were improved or resolved at the time of the last follow-up. Technical aspects and surgical nuances of these approaches for management of intracranial meningiomas are discussed. CONCLUSIONS: With careful preoperative evaluation, keyhole approaches can be utilized singly or in combination to manage meningiomas in a wide variety of locations with satisfactory results

Liana cutting for restoring tropical forests : a rare palaeotropical trial

Liana growth following forest disturbance is threatening the tropical carbon sink by delaying or preventing recov ery. Tree growth can be stimulated by liana cutting; however, its applicability for conservation management remains uncertain, particularly in Africa (the least-studied continent for ecological restoration) and against pervasive barriers such as wildfires. We conducted a small-scale trial to investigate tree sapling regeneration following liana cutting in a lowland African forest prone to low intensity wildfires. We employed a BACI design comprising eighteen 25 m² plots of sapling trees in liana-infested areas. After 5 years of liana cutting, we saw greater recruitment, stem growth and net biomass. Wildfires caused 51% mortality and probably masked liana cutting influences on species and survival, but may have encouraged stem recruitment through interaction with liana cutting. Incorporating our data into a first quantitative review of previous studies, we found that tree growth, recruitment and net growth rates were all consistently higher where lianas were either absent or removed (respectively: 80%, 215%, 633%; n = 14, 3, 4). Tree growth impacts were approximately equivalent across size-classes and continents. We give recommendations for improved plot and sample sizes, but conclude that liana cutting is a promising restoration method for lowland tropical forests, including Africa