bluuebunny/crossref_metadata_2025 huggingface dataset:
Phototoxic effects of two common marine fuels on the settlement success of the coral Acropora tenuis
Authors: Nordborg F. Mikaela , Flores Florita , Brinkman Diane L. , Agustí Susana , Negri Andrew P.
Published: May 2018

Coral reefs are at risk of exposure to petroleum hydrocarbons from shipping spills and uncontrolled discharges during extraction. The toxicity of petroleum hydrocarbons can substantially increase in the presence of ultraviolet radiation (UVR), therefore spills in shallow coral reef environments may be particularly hazardous to reef species. Here we investigated the sensitivity of coral larvae (Acropora tenuis) to dissolved hydrocarbons from heavy fuel oil (HFO) and diesel in the absence and presence of UVR. Larval settlement success decreased with increasing concentrations of dissolved HFO, and co-exposure to UVR doubled the toxicity: 50% effect concentrations (EC50) decreased from 96 (−UVR) to 51 (+UVR) total petroleum aromatic hydrocarbons (TPAH). Toxic thresholds for HFO were similar to concentrations reported during marine spills: EC10s of 24 (−UVR) and 15 (+UVR) µg l−1. While less toxic, diesel also reduced settlement and exhibited phototoxicity: EC10s of 122 (+UVR) and 302 (−UVR) µg l−1. This study demonstrates that the presence of UVR increases the hazard posed by oil pollution to tropical, shallow-water coral reefs. Further research on the effects of oils in the presence of UVR is needed to improve the environmental relevance of risk assessments and ensure appropriate protection for shallow reef environments against oil pollution.
MHD Flow of Sodium Alginate-Based Casson Type Nanofluid Passing Through A Porous Medium With Newtonian Heating
Authors: Khan Arshad , Khan Dolat , Khan Ilyas , Ali Farhad , Karim Faizan ul , Imran Muhammad
Published: May 2018

Casson nanofluid, unsteady flow over an isothermal vertical plate with Newtonian heating (NH) is investigated. Sodium alginate (base fluid)is taken as counter example of Casson fluid. MHD and porosity effects are considered. Effects of thermal radiation along with heat generation are examined. Sodium alginate with Silver, Titanium oxide, Copper and Aluminum oxide are added as nano particles. Initial value problem with physical boundary condition is solved by using Laplace transform method. Exact results are obtained for temperature and velocity fields. Skin-friction and Nusselt number are calculated. The obtained results are analyzed graphically for emerging flow parameters and discussed. It is bring into being that temperature and velocity profile are decreasing with increasing nano particles volume fraction.
A simple methodology for constructing ferromagnetically coupled Cr(iii) compounds
Authors: Fraser Hector W. L. , Smythe Lucy , Dey Sourav , Nichol Gary S. , Piligkos Stergios , Rajaraman Gopalan , Brechin Euan K.
Published: May 2018

Heteroleptic ligands induce ferromagnetic exchange in Cr(iii) dimers.
New synthetic strategies leading to [RNPNR]−anions and the isolation of the [P(Nt-Bu)3]3−trianion
Authors: Vrána Jan , Jambor Roman , Růžička Aleš , Dostál Libor
Published: May 2018

New paths leading to [RNPNR]−anions along with the isolation of the [P(Nt-Bu)3]3−trianion as their lithium derivatives are reported.
Cyto- and geno-toxicity of 1,4-dioxane and its transformation products during ultraviolet-driven advanced oxidation processes
Authors: Li Wei , Xu Elvis , Schlenk Daniel , Liu Haizhou
Published: May 2018

Ultraviolet-driven advanced oxidation processes (UV/AOPs) are integral steps in water reuse treatment trains.
Effect of organic matter on the performance and N2O emission of a granular sludge anammox reactor
Authors: Jia Mingsheng , Castro-Barros Celia M. , Winkler Mari K. H. , Volcke Eveline I. P.
Published: May 2018

A continuously fed bubble column granular sludge anammox reactor was operated for 405 days to investigate the effect of organic matter on the reactor performance and N2O emission.
Elimination of transforming activity and gene degradation during UV and UV/H2O2 treatment of plasmid-encoded antibiotic resistance genes
Authors: Yoon Younggun , Dodd Michael C. , Lee Yunho
Published: May 2018

This study determined deactivation of transforming activity of an ARG and the ARG degradation during UV and UV/H2O2 treatment of plasmid pUC19 containing an ampicillin resistance gene.
Cp*Rh(iii) catalyzed ortho-halogenation of N-nitrosoanilines by solvent-controlled regioselective C–H functionalization
Authors: Peng Qiujun , Hu Jian , Huo Jiyou , Yuan Hongshun , Xu Lanting , Pan Xianhua
Published: May 2018

A highly efficient rhodium-catalyzed, solvent-controlled regioselective C–H halogenation of anilines by using N-nitroso as a suitable and removable directing group was achieved under mild reaction conditions.
Base-mediated 1,6-conjugate addition of the Seyferth–Gilbert reagent to para-quinone methides
Authors: Gupta Ashis Kumar , Ahamad Shakir , Vaishanv Narendra Kumar , Kant Ruchir , Mohanan Kishor
Published: May 2018

An efficient 1,6-conjugate addition reaction of the Seyferth–Gilbert reagent (SGR) to p-quinone methides leading to the synthesis of diarylmethylated diazomethylphosphonates is reported.
Scope of the 2(5H)-furanone helicity rule: a combined ECD, VCD, and DFT investigation
Authors: M. dos Santos Jr. Fernando , Bicalho Keylla U. , Calisto Ítalo H. , S. Scatena Gabriel , Fernandes João B. , Cass Quezia B. , Batista Jr. João M.
Published: May 2018

Combination of ECD, VCD and DFT calculations revealed a possible exception to the widely used helicity rule of the 2(5H)-furanone chromophore.
Roll-to-roll processed, highly conductive, and flexible aluminum (Al) electrodes based on Al precursor inks
Authors: Jung Soo-ho , Choi Dong Yun , Lee Hye Moon
Published: May 2018

R2R machine is designed for the Al thin film coating to the flexible substrate, and the substrate can be applied to the flexible electronics.
An integrated mass spectrometry platform enables picomole-scale real-time electrosynthetic reaction screening and discovery
Authors: Wan Qiongqiong , Chen Suming , Badu-Tawiah Abraham K.
Published: May 2018

A nanoESI mass spectrometry-based reactor/ion source integrated platform enables picomole-scale, online discoveries and mechanistic studies of electrochemical reactions.
Flow-induced voltage generation by driving imidazolium-based ionic liquids over a graphene nano-channel
Authors: Guan Yongji , Shao Qunfeng , Chen Wenqiong , Zhang Jiao , Zhang Xiaoping , Deng Youquan
Published: May 2018

In this study, the flow-induced voltage is investigated by driving the pure bulk room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim][BF4]) flowing over a graphene nano-channel consisting of two parallel single-layered graphene sheets using molecular dynamics simulation for the first time.
Enhancing the antimicrobial and antibiofilm effectiveness of silver nanoparticles prepared by green synthesis
Authors: Oliver Susan , Wagh Harsha , Liang Yuanli , Yang Shuang , Boyer Cyrille
Published: May 2018

Water soluble catechin oligomers produce small (8.5 nm) silver nanoparticles with high antimicrobial and antibiofilm efficacy.
Design of two-dimensional electron gas systems via polarization discontinuity from large-scale first-principles calculations
Authors: Cheng Jianli , Yang Kesong
Published: May 2018

This work demonstrates an efficient approach to design perovskite-oxide-based two dimensional electron gas systems using large-scale first-principles calculations.
Aligned flexible conductive fibrous networks for highly sensitive, ultrastretchable and wearable strain sensors
Authors: Li Guojie , Dai Kun , Ren Miaoning , Wang Yan , Zheng Guoqiang , Liu Chuntai , Shen Changyu
Published: May 2018

A high performance strain sensor based on an aligned conductive fibrous network was prepared with large responsivity, broad sensing range and remarkable stability, demonstrating the applications for detections of both vigorous and subtle human motions.
From interstellar carbon monosulfide to methyl mercaptan: paths of least resistance
Authors: Lamberts T.
Published: May 2018

The 29 reactions linking carbon monosulfide (CS) to methyl mercaptan (CH3SH) via ten intermediate radicals and molecules have been characterized with relevance to surface chemistry in cold interstellar ices. More intermediate species than previously considered are found likely to be present in these ices, such as trans- and cis-HCSH. Both activation and reaction energies have been calculated, along with low-temperature (T > 45 K) rate constants for the radical-neutral reactions. For barrierless radical-radical reactions on the other hand, branching ratios have been determined. The combination of these two sets of information provides, for the first time, quantitative information on the full H + CS reaction network. Early on in this network, that is, early on in the lifetime of an interstellar cloud, HCS is the main radical, while later on this becomes first CH2SH and finally CH3S.
Älterwerden im Beruf – Darstellung einer Gruppenintervention bei mittelalten Pflegekräften
Authors: Maatouk Imad , Helaß Madeleine
Published: May 2018

Der Pflegeberuf unterliegt durch den demografischen Wandel starken Veränderungen, sowohl in der Alterszusammensetzung von Belegschaften, als auch in der Zunahme von multimorbiden, älteren Patienten. Die Prävalenz psychischer Belastung ist bei den Mitarbeitern im Gesundheitswesen bereits heute relativ hoch. Im Zuge der Veränderungen kommt es zu vermehrter psychischer und körperlicher Belastung. Es besteht ein Zusammenhang zwischen zunehmender Belastung und Gedanken an das Ausscheiden aus dem Beruf (intention to leave). Ziel der hier vorgestellten Gruppenintervention war es, eine verhaltenspräventive Maßnahme zur Förderung des gesunden Alterns im Pflegeberuf zur Verfügung zu stellen.
Analysis of Minimally Invasive Left Thoracotomy HVAD Implantation – A Single-Center Experience
Authors: Reichart D. , Brand C.F. , Bernhardt A.M. , Schmidt S. , Schaefer A. , Blankenberg S. , Reichenspurner H. , Wagner F.M. , Deuse T. , Barten M.J.
Published: May 2018

Background Minimally invasive left ventricular assist device (LVAD) implantation may reduce peri-/postoperative complications and risks associated with resternotomies. In this study, we describe our first results using a minimally invasive LVAD implantation technique (lateral thoracotomy [LT] group). These results were compared with LVAD implantations done via full median sternotomy (STX group).

Methods HVAD (HeartWare, Framingham, Massachusetts, United States) implantations in 70 patients (LT group n = 22, 52 ± 15 years old; STX group n = 48, 59 ± 11 years old) were retrospectively analyzed. Minimally invasive access via left thoracotomy was feasible in 22 patients. Peri- and postoperative analyses of survival and adverse events were performed.

Results No survival differences were observed between the LT and STX group (p = 0.43). LT patients without temporary right ventricular assist device (tRVAD) showed a significantly better survival rate compared to LT patients with concomitant tRVAD implantation (p = 0.02), which could not be demonstrated in the STX group (p = 0.11). Two LT and four STX patients were successfully bridged to heart transplantation and three STX patients were successfully weaned with subsequent LVAD explantations. LVAD-related infections (n = 4 LT group vs n = 20 STX group, p = 0.04) were less likely in the LT group. No wound dehiscence occurred in the LT group, whereas five were observed in the STX group (p = 0.17). The amount of perioperative blood transfusions (within the first 7 postoperative days) did not differ in both study groups (p = 0.48).

Conclusion The minimally invasive approach is a viable alternative with the possibility to reduce complications and should be particularly considered for bridge-to-transplant patients.
Neuroprotective Strategies in Repair and Replacement of the Aortic Arch
Authors: Mullan Clancy , Catalano Michael , Manetta Frank
Published: May 2018

Aortic arch surgery is a technical challenge, and cerebral protection during distal anastomosis is a continued topic of controversy and discussion. The physiologic effects of hypothermic arrest and adjunctive cerebral perfusion have yet to be fully defined, and the optimal strategies are still undetermined. This review highlights the historical context, physiological rationale, and clinical efficacy of various neuroprotective strategies during arch operations.
Study of the cells proliferating in parent versus F hybrid mixed lymphocyte culture.
Authors: Piguet P F , Dewey H K , Vassalli P
Published: May 2018

Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.
Who Will Pay for Increasing Biofuel Mandates? Incidence of the Renewable Fuel Standard Given a Binding Blend Wall
Authors: Korting Christina , de Gorter Harry , Just David R.
Published: May 2018

We show that the cost of increasing biofuel mandates given a binding ethanol blend wall falls disproportionately on diesel fuel consumers. The extent of the burden on diesel fuel consumers is explained neither by their relatively more inelastic demand nor by blenders seeking to capitalize on the biodiesel tax credit. Relaxing the blend wall constraint by increasing the potential demand for high‐ethanol blends is the only effective lever to insulate diesel fuel drivers from the one‐sided welfare impacts of rising mandate levels. The independent effects of the nested mandate structure and the joint compliance base under the Renewable Fuel Standard (RFS) generate the link between motor gasoline and diesel fuel markets. Our results highlight the importance of evaluating the incidence of the RFS in a holistic framework taking both ethanol and biodiesel into account.
PERFect: PERmutation Filtering test for microbiome data
Authors: Smirnova Ekaterina , Huzurbazar Snehalata , Jafari Farhad
Published: May 2018

The human microbiota composition is associated with a number of diseases including obesity, inflammatory bowel disease, and bacterial vaginosis. Thus, microbiome research has the potential to reshape clinical and therapeutic approaches. However, raw microbiome count data require careful pre-processing steps that take into account both the sparsity of counts and the large number of taxa that are being measured. Filtering is defined as removing taxa that are present in a small number of samples and have small counts in the samples where they are observed. Despite progress in the number and quality of filtering approaches, there is no consensus on filtering standards and quality assessment. This can adversely affect downstream analyses and reproducibility of results across platforms and software. We introduce PERFect, a novel permutation filtering approach designed to address two unsolved problems in microbiome data processing: (i) define and quantify loss due to filtering by implementing thresholds and (ii) introduce and evaluate a permutation test for filtering loss to provide a measure of excessive filtering. Methods are assessed on three “mock experiment” data sets, where the true taxa compositions are known, and are applied to two publicly available real microbiome data sets. The method correctly removes contaminant taxa in “mock” data sets, quantifies and visualizes the corresponding filtering loss, providing a uniform data-driven filtering criteria for real microbiome data sets. In real data analyses PERFect tends to remove more taxa than existing approaches; this likely happens because the method is based on an explicit loss function, uses statistically principled testing, and takes into account correlation between taxa. The PERFect software is freely available at https://github.com/katiasmirn/PERFect.
Oxygen-dependent regulation of immune checkpoint mechanisms
Authors: Ohta Akio
Published: May 2018

Immunotherapy of cancer has finally materialized following the success of immune checkpoint blockade. Since down-regulation of immune checkpoint mechanisms is beneficial in cancer treatment, it is important to ask why tumors are infamously filled with the immunosuppressive mechanisms. Indeed, immune checkpoints are physiological negative feedback mechanisms of immune activities, and the induction of such mechanisms is important in preventing excessive destruction of inflamed normal tissues. A condition commonly found in tumors and inflamed tissues is tissue hypoxia. Oxygen deprivation under hypoxic conditions by itself is immunosuppressive because proper oxygen supply could support bioenergetic demands of immune cells for optimal immune responses. However, importantly, hypoxia has been found to up-regulate a variety of immune checkpoints and to be able to drive a shift toward a more immunosuppressive environment. Moreover, extracellular adenosine, which accumulates due to tissue hypoxia, also contributes to the up-regulation of other immune checkpoints. Taken together, tissue oxygen is a key regulator of the immune response by directly affecting the energy status of immune effectors and by regulating the intensity of immunoregulatory activity in the environment. The regulators of various immune checkpoint mechanisms may represent the next focus to modulate the intensity of immune responses and to improve cancer immunotherapy.
The Impact of Different Postgraduate Year Training in Neurosurgery Residency on 30-Day Postoperative Outcomes
Authors: Macki Mohamed , Fakih Mohamed , Rubinfeld Ilan , Chang Victor , Walters Beverly C
Published: May 2018

BACKGROUND

Previous studies have failed to demonstrate statistically significant differences in postsurgical outcomes between operative cases featuring resident participation compared to attending only; however, the effects of level of postgraduate year (PGY) training have not been explored.

OBJECTIVE

To correlate different PGYs in neurosurgery with 30-d postoperative outcomes.

METHODS

Using National Surgical Quality Improvement Program 2005–2014, adult neurosurgical cases were divided into subspecialties: spine, open-vascular, cranial, and functional in teaching institutions. Comparison groups: cases involving junior residents (PGY 1–PGY 3), mid-level residents (PGY 4 + PGY 5), and senior residents (PGY 6 + PGY 7). Primary outcome measures included any wound disruption (surgical site infections and/or wound dehiscence), Clavien-Dindo grade IV (life-threatening) complications, and death.

RESULTS

Compared to junior residents (n = 3729) and mid-level residents (n = 2779), senior residents (n = 3692) operated on patients with a greater comorbidity burden, as reflected by higher American Society of Anesthesiology classifications and decreased level of functional status. Cases with senior resident participation experienced the highest percentages of postoperative wound complications (P = .005), Clavien-Dindo grade IV complications (P = .001), and death (P = .035). However, following multivariable regression, level of residency training in neurosurgery did not predict any of the 3 primary outcome measures. Compared to spinal cases, cranial cases predicted a higher incidence of life-threatening complications (odds ratio 1.84, P < .001).

CONCLUSION

Cases in the senior resident cohort were more technically challenging and exhibited a higher comorbidity burden preoperatively; however, level of neurosurgical training did not predict any wound disruption, life-threatening complications, or death. Residents still provide safe and effective assistance to attending neurosurgeons.
Endonasal Suturing of Nasoseptal Flap to Nasopharyngeal Fascia Using the V-Loc™ Wound Closure Device: 2-Dimensional Operative Video
Authors: Zwagerman Nathan T , Geltzeiler Mathew N , Wang Eric W , Fernandez-Miranda Juan C , Snyderman Carl H , Gardner Paul A
Published: May 2018

We present a case of cerebrospinal fluid (CSF) leak after endoscopic endonasal resection of a large clival chordoma in an obese patient. The leak was at the lower reconstruction at the craniocervical junction and had failed repositioning. Using the V-Loc™ wound closure device (Covidien, New Haven, Connecticut) to suture the nasoseptal flap to the nasopharyngeal fascia, a water-tight seal was created and, along with a lumbar drain, the patient healed successfully.

CSF leak after an endoscopic endonasal approach (EEA) to intradural pathologies remains one of the more common complications.
1-4
Various closure techniques have been developed
5-8
with success in mitigating this risk, but all have their limitations and rely on multiple layers including vascularized flaps like the nasoseptal flap.
9-11
Endonasal suturing of graft materials offers the advantage of creating a water-tight seal. We present the use of the V-Loc™ wound closure device (Covidien) to successfully seal a postoperative CSF leak. The absorbable V-Loc™ wound closure device does not require the surgeon to tie knots, which is the most challenging step in a deep, 2-dimensional corridor. The suture is barbed and is anchored by threading the needle through a prefabricated loop at the end of the suture which locks in place. Each throw of the suture through tissue maintains the suture line as the barbs catch the tissue and prevent retraction. After successful closure, the needle can simply be cut off.

The V-Loc™ wound closure device (Covidien) is a safe and effective adjunct to reconstruction after endoscopic endonasal skull base surgery as it provides an option for graft/flap suturing.

A written release from the patient whose name or likeness is submitted as part of this Work is on file.
Reasons for Opioid Discontinuation and Unintended Consequences Following Opioid Discontinuation Within the TOPCARE Trial
Authors: Husain Jawad M , LaRochelle Marc , Keosaian Julia , Xuan Ziming , Lasser Karen E , Liebschutz Jane M
Published: May 2018

Objective

To identify reasons for opioid discontinuation and post-discontinuation outcomes among patients in the Transforming Opioid Prescribing in Primary Care (TOPCARE) study.

Design

In TOPCARE, an intervention to improve adherence to opioid prescribing guidelines, randomized intervention primary care providers (PCPs) received nurse care manager support, an electronic registry, academic detailing, and electronic tools, and control PCPs received electronic tools only.

Setting

Four Boston safety net primary care practices.

Subjects

Patients in both TOPCARE study arms who discontinued opioid therapy during the trial.

Methods

Through chart review, we examined the reason for discontinuation and post-discontinuation outcomes: one or more PCP visits, one or more pain-related emergency department (ED) visits, evidence of opioid use disorder (OUD), and referral for OUD treatment.

Results

Opioid discontinuations occurred in 83/586 (14.2%) intervention and 42/399 (10.5%) control patients (P = 0.09). Among patients who discontinued opioids, 81 (65%) discontinued for misuse, with no difference by group (P = 0.38). Aberrancy in monitoring (e.g., discordant urine drug test results) was the most common type of misuse prompting discontinuation (occurring in (51/83 [61%] of intervention patients vs 19/42 [45%, P = 0.08] of control patients). Intervention patients who discontinued opioids had less PCP follow-up (65% vs 88%, P < 0.01) compared with control patients. We found no differences between groups for pain-related ED visits, evidence of OUD, or OUD treatment referral following discontinuation.

Conclusions

The decreased follow-up among TOPCARE intervention patients who discontinued opioids highlights the need to understand unintended consequences of involuntary opioid discontinuations resulting from interventions to reduce opioid risk.
Household Production in an Egalitarian Society
Authors: Onozaka Yuko , Hafzi Kamran
Published: May 2018

Norwegian national policies strongly incentivize double-earner households and gender equality, but various gender gaps persist both at work and at home. In these seemingly contradictory situations, what are the mechanisms under which Norwegian households allocate their market and domestic labor? Drawing on both a large set of administrative data and a representative survey, this question is examined from two perspectives. First, we focus on the micro-economic processes and investigate if Norwegian households act according to economic rationality or if they still follow the gender norm “A man should earn more than his wife.” Second, we focus on how Norway’s contextual factors may influence the household experiences when a wife has better market productivity. We find that a wife with better market productivity, who is thereby facing the risk of outearning her husband, works more hours and earns more than her husband, while doing less chores—behavior consistent with economic rationality. Further analyses show that women’s “higher” relative market productivity is mainly a consequence of having low-income husbands, and “higher” and “lower” market productivity women are surprisingly similar in other sociodemographic aspects. Norwegian redistribution policies, through progressive taxation and benefit transfers, seem to mitigate the income differences and promote gender neutrality in a sense that if couples wish to pursue an untraditional division, by preference or by necessity, they seem to be able to do so without being held back by the traditional gender expectations or being very poor.
Outcomes and subjective assessment of rotation-plasty in patients with proximal femoral focal deficiency
Authors: Kowalczyk Bart , Kuźnik-Buziewicz Anna
Published: May 2018

This study presents outcomes of rotation-plasty for unilateral proximal femoral focal deficiency in the adolescent population. The function, timing of knee fusion, and complications were presented as well as patients’ assessment of their function and appearance. Eight patients, aged 8.37 years (range: 3–16 years) during surgery, were evaluated. The mean follow-up duration was 9.25 years (range: 6–12 years). At follow-up, all the patients were pain free and able to ambulate outdoors. Complications included derotation of the foot in five patients, necessitating a re-rotation osteotomy in two. All patients accepted their appearance, considering the rotation-plasty beneficial for their functional status.
Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain
Authors: Chen Shuhua , Kumar Narender , Mao Zisu , Sitruk-Ware Regine , Brinton Roberta Diaz
Published: May 2018

Objective:

Neurogenesis is the principal regenerative mechanism to sustain the plasticity potential in adult brains. Decreased neurogenesis parallels the cognition decline with aging, and has been suggested as a common hallmark in the progression of many neurodegeneration diseases. We previously reported that acute exposure to segesterone acetate (ST-1435; Nestorone), alone or in combination with 17β-estradiol (E2), increased human neural stem cells proliferation and survival both in vitro and in vivo. The present study expanded our previous findings to investigate the more clinical related chronic exposure in combination with E2on the regenerative capacity of adult brain.

Methods:

To mimic the chronic contraception exposure in women, 3-month old female mice (n = 110) were treated with ST-1435, with or without co-administration of E2, for 4 weeks. Neural cell proliferation and survival, and oligodendrocyte generation were assessed. The involvement of insulin-like growth factor 1 signaling was studied.

Results:

Our results demonstrated that chronic ST-1435 and E2alone or in combination increased neurogenesis by a comparable magnitude, with minimum to no antagonistic or additive effects between ST-1435 and E2. In addition, chronic exposure of ST-1435 or ST-1435 + E2stimulated oligodendrocyte generation, indicating potential elevated myelination. Insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) were also up-regulated after chronic ST-1435 and E2exposure, suggesting the involvement of IGF-1 signaling as the potential underlined regulatory pathway transducing ST-1435 effect.

Conclusion:

These findings provide preclinical evidence and mechanistic insights for the development of ST-1435 as a neuroregenerative therapy to promote intrinsic regenerative capacity in female brains against aging and neurodegenerative disorders.
Menopausal hormone therapy and mild cognitive impairment: a randomized, placebo-controlled trial
Authors: Yoon Byung-Koo , Chin Juhee , Kim Jong-Won , Shin Myung-Hee , Ahn Soohyun , Lee Dong-Yun , Seo Sang Won , Na Duk L.
Published: May 2018

Objective:

The aim of the study was to explore the therapeutic potential of menopausal hormone therapy (MHT) in women with mild cognitive impairment (MCI).

Methods:

Thirty-seven postmenopausal women (age range: 57-82 y) with multiple-domain, amnestic subtype MCI were randomly assigned to either placebo (n = 18) or MHT (n = 19) for 24 months (percutaneous estradiol [E2] gel [0.1%, 2 mg/d] and oral micronized progesterone [MP4] [100 mg/d]). All participants received donepezil, and apolipoprotein E genotype was determined. The primary endpoint was general cognitive function: Alzheimer's disease Assessment Scale, cognitive subscale, the Korean version of Mini-Mental State Examination (K-MMSE), and the Korean version of the Montreal Cognitive Assessment (MoCA_K) were performed in-person every 6 months.

Results:

Twenty-one participants (placebo 13, MHT 8) completed the trial (56.8%). Progression rates to dementia were 52.9% (9/17) in the placebo group and 44.4% (8/18) in the MHT group. Within-group analysis showed that all three tests significantly worsened during the trial in the placebo, but not the MHT groups. Analysis adjusted for ε4 allele demonstrated that MHT significantly reduced deterioration of MoCA_K score, a sensitive tool for assessing global cognition in MCI (P = 0.0261). Compared with the control group, both MoCA_K (P = 0.043; mean difference, 3.85; 95% CI, −0.46 to 8.16) and K-MMSE (P = 0.0319; mean difference, 3.26; 95% CI, 0.04-6.48) scores were significantly better at 24 months in the MHT group.

Conclusions:

Long-term MHT using percutaneous E2 gel and oral MP4 might attenuate cognitive decline in postmenopausal women with MCI.
Labile haemoglobin as a glycaemic biomarker for patient-specific monitoring of diabetes: mathematical modelling approach
Authors: León-Triana O. , Calvo G. F. , Belmonte-Beitia J. , Rosa Durán M. , Escribano-Serrano J. , Michan-Doña A. , Pérez-García V. M.
Published: May 2018

Diabetes mellitus constitutes a major health problem and its clinical presentation and progression may vary considerably. A number of standardized diagnostic and monitoring tests are currently used for diabetes. They are based on measuring either plasma glucose, glycated haemoglobin or both. Their main goal is to assess the average blood glucose concentration. There are several sources of interference that can lead to discordances between measured plasma glucose and glycated haemoglobin levels. These include haemoglobinopathies, conditions associated with increased red blood cell turnover or the administration of some therapies, to name a few. Therefore, there is a need to provide new diagnostic tools for diabetes that employ clinically accessible biomarkers which, at the same time, can offer additional information allowing us to detect possible conflicting cases and to yield more reliable evaluations of the average blood glucose level concentration. We put forward a biomathematical model to describe the kinetics of two patient-specific glycaemic biomarkers to track the emergence and evolution of diabetes: glycated haemoglobin and its labile fraction. Our method incorporates erythrocyte age distribution and utilizes a large cohort of clinical data from blood tests to support its usefulness for diabetes monitoring.
Tracking data and retrospective analyses of diet reveal the consequences of loss of marine subsidies for an obligate scavenger, the Andean condor
Authors: Lambertucci Sergio A. , Navarro Joan , Sanchez Zapata José A. , Hobson Keith A. , Alarcón Pablo A. E. , Wiemeyer Guillermo , Blanco Guillermo , Hiraldo Fernando , Donázar José A.
Published: May 2018

Over the last century, marine mammals have been dramatically reduced in the world's oceans. We examined evidence that this change caused dietary and foraging pattern shifts of the Andean condor (
Vultur gryphus
) in Patagonia. We hypothesized that, after the decrease in marine mammals and the increase in human use of coastlines, condor diet changed to a more terrestrial diet, which in turn influenced their foraging patterns. We evaluated the diet by means of stable isotope analysis (
δ
13
C,
δ
15
N and
δ
34
S) of current (last decade) and historical (1841–1933) feathers. We further evaluated the movement patterns of 23 condors using satellite tracking of individuals. Condors reduced their use of marine-derived prey in recent compared with historical times from 33 ± 13% to less than 8 ± 3% respectively; however, they still breed close to the coast. The average distance between the coast and nests was 62.5 km, but some nests were located close to the sea (less than 5 km). Therefore, some birds must travel up to 86 km from nesting sites, crossing over the mountain range to find food. The worldwide reduction in marine mammal carcasses, especially whales, may have major consequences on the foraging ecology of scavengers, as well as on the flux of marine inputs within terrestrial ecosystems.
D-amino acid-mediated translation arrest is modulated by the identity of the incoming aminoacyl-tRNA
Authors: Fleisher Rachel C. , Cornish Virginia W. , Gonzalez Ruben L.
Published: May 2018

A complete understanding of the determinants that restrict D-amino acid incorporation by the ribosome, which is of interest to both basic biologists as well as the protein engineering community, remains elusive. Previously, we demonstrated that D-amino acids are successfully incorporated into the C-terminus of the nascent polypeptide chain. Ribosomes carrying the resulting peptidyl-D-aminoacyl-tRNA (peptidyl-D-aa-tRNA) donor substrate, however, partition into subpopulations that either undergo translation arrest through inactivation of the ribosomal peptidyl-transferase center (PTC) or remain translationally competent. The proportion of each subpopulation is determined by the identity of the D-amino acid sidechain. Here, we demonstrate that the identity of the aminoacyl-tRNA (aa-tRNA) acceptor substrate that is delivered to ribosomes carrying a peptidyl-D-aa-tRNA donor further modulates this partitioning. Our discovery demonstrates that it is the pairing of the peptidyl-D-aa-tRNA donor and the aa-tRNA acceptor that determines the activity of the PTC. Moreover, we provide evidence that both the amino acid and tRNA components of the aa-tRNA donor contribute synergistically to the extent of arrest. The results of this work deepen our understanding of the mechanism of D-amino acid-mediated translation arrest and how cells avoid this precarious obstacle, reveal similarities to other translation arrest mechanisms involving the PTC, and provide a new route for improving the yields of engineered proteins containing D-amino acids.
Autonomous functionality of an upstream open reading frame in polycistronic mammalian mRNAs
Authors: Kitano Shohei , Pratt Gabriel , Takao Keizo , Aizawa Yasunori
Published: May 2018

Upstream open reading frames (uORFs) are established as cis-acting elements for eukaryotic translation of annotated ORFs (anORFs) located on the same mRNAs. Here, we identified a mammalian uORF with functions that are independent from anORF translation regulation. Bioinformatics screening using ribosome profiling data of human and mouse brains yielded 308 neurologically vital genes from which anORF and uORFs are polycistronically translated in both species. Among them, Arhgef9 contains a uORF named SPICA, which is highly conserved among vertebrates and stably translated only in specific brain regions of mice. Disruption of SPICA translation by ATG-to-TAG substitutions did not perturb translation or function of its anORF product, collybistin. SPICA-null mice displayed abnormal maternal reproductive performance and enhanced anxiety-like behavior, characteristic of ARHGEF9-associated neurological disorders. This study demonstrates that mammalian uORFs can be independent genetic units, revising the prevailing dogma of the monocistronic gene in mammals, and even eukaryotes.
Alternative activation of macrophages is accompanied by chromatin remodeling and short-term dampening of macrophage secondary response
Authors: Tang Mei San , Miraldi Emily R. , Girgis Natasha M. , Bonneau Richard A. , Loke P’ng
Published: May 2018

Interleukin-4 (IL-4) activates macrophages to adopt a distinct phenotype associated with clearance of helminth infections and tissue repair. Here, we describe changes in the accessible chromatin landscape following IL-4 stimulation of terminally differentiated mouse peritoneal macrophages. This chromatin remodeling process occurs in both tissue resident and monocyte-derived macrophages, but the regions gaining accessibility post-stimulation are macrophage-specific. PU.1 motif is similarly associated with tissue resident and monocyte-derived IL-4 induced regions, but has macrophage-specific DNA shape and predicted co-factors. In addition, IL-4 stimulation leads to short-term dampening of macrophage secondary response. However, the degree of dampening differs between macrophages derived from different genetic backgrounds. Together, these results lead us to propose that DNA sequence variations can alter parts of the accessible chromatin landscape and differences in secondary responses due to host genetics can contribute to phenotypic variations in immune responses.
ClusterMap: Comparing analyses across multiple Single Cell RNA-Seq profiles
Authors: Gao Xin , Hu Deqing , Gogol Madelaine , Li Hua
Published: May 2018

Single cell RNA-Seq facilitates the characterization of cell type heterogeneity and developmental processes. Further study of single cell profiles across different conditions enables the understanding of biological processes and underlying mechanisms at the sub-population level. However, developing proper methodology to compare multiple scRNA-Seq datasets remains challenging. We have developed ClusterMap, a systematic method and workflow to facilitate the comparison of scRNA profiles across distinct biological contexts. Using hierarchical clustering of the marker genes of each sub-group, ClusterMap matches the sub-types of cells across different samples and provides “similarity” as a metric to quantify the quality of the match. We introduce a purity tree cut method designed specifically for this matching problem. We use Circos plot and regrouping method to visualize the results concisely. Furthermore, we propose a new metric “separability” to summarize sub-population changes among all sample pairs. In three case studies, we demonstrate that ClusterMap has the ability to offer us further insight into the different molecular mechanisms of cellular sub-populations across different conditions. ClusterMap is implemented in R and available at https://github.com/xgaoo/ClusterMap.
Real-time projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018
Authors: Kelly J. Daniel , Worden Lee , Wannier Rae , Hoff Nicole A. , Mukadi Patrick , Sinai Cyrus , Ackley Sarah , Chen Xianyun , Gao Daozhou , Selo Bernice , Mossoko Mathais , Okitolonda-Wemakoy Emile , Richardson Eugene T. , Rutherford George W. , Lietman Thomas M. , Muyembe-Tamfum Jean Jacques , Rimoin Anne W. , Porco Travis C.
Published: May 2018

Background

As of May 27, 2018, 54 cases of Ebola virus disease (EVD) were reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the current outbreak size and duration with and without vaccine use.

Methods

We modeled Ebola virus transmission using a stochastic branching process model with a negative binomial distribution, using both estimates of reproduction number R declining from supercritical to subcritical derived from past Ebola outbreaks, as well as a particle filtering method to generate a probabilistic projection of the future course of the outbreak conditioned on its reported trajectory to date; modeled using 0%, 44%, and 62% estimates of vaccination coverage. Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize a regression model predicting the outbreak size from the number of observed cases from April 4 to May 27.

Results

With the stochastic transmission model, we projected a median outbreak size of 78 EVD cases (95% credible interval: 52, 125.4), 86 cases (95% credible interval: 53, 174.3), and 91 cases (95% credible interval: 52, 843.5), using 62%, 44%, and 0% estimates of vaccination coverage. With the regression model, we estimated a median size of 85.0 cases (95% prediction interval: 53.5, 216.6).

Conclusions

This outbreak has the potential to be the largest outbreak in DRC since 2007. Vaccines are projected to limit outbreak size and duration but are only part of prevention, control, and care strategies.
General Regulatory Factors control the fidelity of transcription by restricting non-coding and ectopic initiation
Authors: Challal Drice , Barucco Mara , Kubik Slawomir , Feuerbach Frank , Candelli Tito , Geoffroy Hélène , Benaksas Chaima , Shore David , Libri Domenico
Published: May 2018

The fidelity of transcription initiation is essential for accurate gene expression, but the determinants of start site selection are not fully understood. Rap1 and other General Regulatory Factors (GRFs) control the expression of many genes in yeast. We show that depletion of these factors induces widespread ectopic transcription initiation within promoters. This generates many novel non-coding RNAs and transcript isoforms with diverse stability, profoundly altering the coding potential of the transcriptome. Ectopic transcription initiation strongly correlates with altered nucleosome positioning. We show that Rap1 sterically constrains nucleosomes as its mere binding to the DNA can be sufficient for restoration normal nucleosome positioning, transcription initiation and gene expression. These results demonstrate an essential role for GRFs in the fidelity of transcription initiation and in the suppression of pervasive transcription, redefining current models of their function. They have general implications for the mechanism of transcription initiation and the control of gene expression.

HIGHLIGHTS

Rap1, Abf1 and Reb1 control the fidelity of transcription initiation and suppress pervasive transcription

Widespread ectopic transcription initiation in Rap1-deficient cells induces variegated alterations in gene expression

Altered nucleosome positioning in GRFs-defective cells correlate with ectopic transcription initiation.

Rap1 controls nucleosomes positioning and transcription initiation at least partially by a steric hindrance mechanism
Quenching an active swarm: Effects of light exposure on collective motility in swarmingSerratia marcescenscolonies
Authors: Patteson Alison E , Yang Junyi , Arratia Paulo E , Gopinath Arvind
Published: May 2018

Swarming colonies of the light responsive bacteriaSerratia marcescensgrown on agar exhibit robust fluctuating large-scale collective flows that include arrayed vortices, jets, and sinuous streamers. We study the immobilization and quenching of these large-scale flows when the moving swarm is exposed to light with a substantial ultra-violet component. We map the response to light in terms of two independent parameters - the light intensity and duration of exposure and identify the conditions under which mobility is affected significantly. For small exposure times and/or low intensities, we find collective mobility to be negligibly affected. Increasing exposure times and/or intensity to higher values temporarily suppresses collective mobility. Terminating exposure allows bacteria regain motility and eventually reestablish large scale flows. For long exposure times or at high intensities, exposed bacteria become paralyzed, with macroscopic speeds eventually reducing to zero. In this process, they form highly aligned, jammed domains. Individual domains eventually coalesce into a large macroscopic domain with mean radial extent growing as the square root of exposure time. Post exposure, active bacteria dislodge exposed bacteria from these jammed configurations; initial dissolution rates are found to be strongly dependent on duration of exposure suggesting that caging effects are substantial at higher exposure times. Based on our experimental observations, we propose a minimal Brownian dynamics model to examine the escape of exposed bacteria from the region of exposure. Our results complement studies on planktonic bacteria and inform models for pattern formation in gradated illumination.