bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate-conjugated liposomal docetaxel reverses multidrug resistance in breast cancer cells
Authors: Li Na , Fu Tingting , Fei Wenling , Han Tianyan , Gu Xiangshuai , Hou Yanhui , Liu Yanhua , Yang Jianhong
Published: June 2019

Objectives

Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated docetaxel-loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE-mPEG-coated liposomes (stealth liposomes) and commercial Taxotere®.

Key findings

Liposomes were prepared by thin – film dispersion method. Evaluations were performed using human breast cancer MCF-7 and resistant MCF-7/ADR cells. The reversal multidrug-resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay.

Results

The TPGS-chol-liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (−0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS-coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS-coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P-glycoprotein.

Conclusions

The TPGS-conjugated liposomes showed significant advantages in vitro compared with the PEG-conjugated liposomes. The TPGS-conjugated liposomes could reverse the MDR and enhance breast cancer therapy.
Redefining Language Death: Evidence From Moribund Grammars
Authors: Bousquette Joshua , Putnam Michael T.
Published: June 2019

The present work presents a critical assessment of claims in recent literature that moribund language varieties exhibit accelerated language decay, and that attrition in individual grammars has a causational relationship with language shift to the majority language. We show these claims to be unfounded. Based on two empirical points taken from moribund heritage varieties of German—complementizer agreement and the restructuring of the morphosyntactic properties of dative case—we provide evidence that (a) attrition in the form of simplification of the heritage grammar is often times minimal, especially when compared to the nonstandard input varieties (rather than to Standard German), and (b) that systematic restructuring of the grammar is a typological pattern in language contact settings. These empirical findings point toward the limited effects of attrition on particular domains of grammar systems across the lifespan.
Learners’ English Vocabulary Knowledge Prior to Formal Instruction: The Role of Learner‐Related and Word‐Related Variables
Authors: Puimège Eva , Peters Elke
Published: June 2019

This study focused on the mechanisms underlying incidental second language (L2) vocabulary acquisition prior to formal instruction. We designed a cross‐sectional study to examine which learner‐related and word‐related variables affect young learners’ vocabulary knowledge at the level of meaning recognition and meaning recall. We collected data from 616 Flemish children between 10 and 12 years old by using a questionnaire about learners’ extramural English, an English vocabulary test, and a Dutch vocabulary test. The findings revealed that participating learners frequently engaged in activities involving English before receiving formal instruction and that their amount of extramural English increased with age. The results also showed the rate of vocabulary growth from exposure to extramural English for three contiguous age groups. Further, both word‐related and learner‐related variables predicted vocabulary knowledge. Cognateness was the most powerful predictor, followed by frequency and concreteness. We also found a positive relationship between extramural English and vocabulary knowledge.

Open Practices

This article has been awarded an Open Materials badge. All materials are publicly accessible via the IRIS Repository at https://www.iris-database.org. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
A global perspective for biodiversity history with ancient environmental DNA
Authors: Epp Laura S.
Published: June 2019

The past centuries have seen tremendous turnovers in species distributions and biodiversity due to anthropogenic impacts on a global scale. The processes are ongoing and mostly not well documented. Long‐term records of biotic change can be recovered from sedimentary deposits, but traditional analyses were restricted to organisms that leave behind visible traces and molecular genetic tools were mostly employed on samples that promised good DNA preservation. In this issue of Molecular Ecology, Shaw, Weyrich, Hallegraeff and Cooper (2019) and Gomez Cabrera et al. (2019) present two studies on marine sedimentary records from warm environments, in which they successfully analyze ancient environmental DNA (aeDNA) on a decadal and centennial scale. Notably, the studies were conducted on novel samples with nonoptimal preservation conditions for ancient DNA ‐ historical collections of ship ballast tank sediments from Australia and two coral reef cores spanning up to 750 years (Figure 1) ‐ but yielded a high diversity of taxa. This highlights that aeDNA is a promising tool to globally study biodiversity history on scales of decades to centuries ‐ the timeframe most relevant to human society in the context of both current climate change and direct anthropogenic modifications of the environment.
Morphometric analysis of Chilean blue whales and implications for their taxonomy
Authors: Pastene Luis A. , Acevedo Jorge , Branch Trevor A.
Published: June 2019

In the Southern Hemisphere, blue whales are currently divided into two subspecies, Antarctic blue whales (Balaenoptera musculus intermedia) and pygmy blue whales (B. m. brevicauda), but there is some debate about whether Chilean blue whales should also be considered as a separate subspecies. Here, we provide novel morphometric data to directly address this taxonomic question from a biological survey of 60 blue whales taken during the 1965/1966 Chilean whaling season. The data show that maximum body length and mean body length of both sexually mature females and males for Chilean blue whales are intermediate between pygmy and Antarctic blue whales; and that fluke‐anus lengths of Chilean blue whales are significantly different from pygmy blue whales, but not necessarily from Antarctic blue whales. There is also some support from the data that snout‐eye measurements are different among all three groups. These data provide further confirmation that Chilean blue whales are a distinct population requiring separate management from other blue whale populations, and are also consistent with suggestions that Chilean blue whales are not the same subspecies as pygmy blue whales.
Neural mechanisms underlying adaptive and maladaptive consequences of stress: Roles of dopaminergic and inflammatory responses
Authors: Furuyashiki Tomoyuki , Kitaoka Shiho
Published: June 2019

Stress caused by adverse and demanding conditions, a risk factor for mental illnesses, induces adaptive or maladaptive neural and behavioral consequences, depending on the conditions. Studies using rodent stress models have revealed multiple mechanisms related to dopamine and inflammation for stress‐induced neural and behavioral changes. Thus, repeated stress alters activities of ventral tegmental area dopamine neurons projecting to the nucleus accumbens and the medial prefrontal cortex in distinct manners. In the nucleus accumbens, repeated stress decreases activities of D1 receptor‐expressing neurons. In the medial prefrontal cortex, single stress increases dopamine D1 receptor signaling, leading to dendritic hypertrophy of excitatory neurons and stress resilience. These changes are attenuated with repetition of stress via prostaglandin E2, an inflammation‐related lipid mediator. Repeated stress activates microglia in the medial prefrontal cortex and the hippocampus. Innate immune receptors, such as the toll‐like receptor 2/4 and P2X7, are crucial for repeated stress‐induced microglial activation, leading to neural and behavioral changes through proinflammatory cytokines. In addition, repeated stress induces monocyte infiltration to the brain, and impairs the blood–brain barrier in the nucleus accumbens, leading to cytokine leakage to the brain. These monocyte‐derived responses are involved in stress‐induced behavioral changes. These findings show crucial roles of the accumbal and prefrontal dopamine pathways and inflammatory responses in the brain and body to direct adaptive and maladaptive consequences of stress, and pave the way for identifying a neural origin of stress and understanding the stress‐related pathology of mental illnesses.
Neonatal osteoma cutis due to a mutation in GNAS
Authors: Levy‐Shraga Yael , Barel Ortal , Javasky Elisheva , Barzilai Aviv , Greenberger Shoshana
Published: June 2019

We describe a 4‐week‐old baby boy who presented with white firm cutaneous nodules and failure to thrive. He did not have dysmorphic features, and laboratory tests including serum calcium, phosphorous, thyroid function, and parathyroid hormone level were within normal ranges. Whole exome sequencing revealed an inactivating mutation in GNAS that was previously described as causing pseudohypoparathyroidism.
Cutaneous involvement of polymorphic post‐transplant lymphoproliferative disorder in a child after liver transplantation
Authors: Chen Kuan‐Yu , Lin Chien‐Yio , Kuo Tseng‐tong , Shih Lee‐Yung , Chang Chih‐Hao , Chen Wei‐Ti , Yang Chin‐Yi
Published: June 2019

Post‐transplantation lymphoproliferative disorder (PTLD) is one of the most common de novo malignancies in patients who receive immunosuppressive therapy after solid organ transplantation. We report a case of a 5‐year‐old girl who presented with indurated violaceous skin nodules 3.5 years post–liver transplantation, diagnosed as polymorphic PTLD, also involving Waldeyer's ring, spleen, and multiple lymph nodes. Through reduction of immunosuppression, most of the lesions resolved and the liver allograft was preserved.
Vocal cord inflammatory myofibroblastic tumor with mucoid deposits harboring TIMP3–ALK fusion: A potential diagnostic pitfall
Authors: Yorita Kenji , Togashi Yuki , Nakagawa Hideyuki , Miyazaki Katsushi , Sakata Seiji , Baba Satoko , Takeuchi Kengo , Hayashi Yoshihiro , Murakami Ichiro , Kuroda Naoto , Oda Yoshinao , Kohashi Kenichi , Yamada Yuichi , Kiyozawa Daisuke , Michal Michael , Michal Michal
Published: June 2019

A 35‐year‐old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two‐thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion‐like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well‐differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3–ALK fusion was confirmed by 5′ rapid ampliﬁcation of cDNA ends. We diagnosed the lesion as an IMT, and an ALK‐rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.
The Expat Gap: Are Local‐Born Entrepreneurs in Developing Countries at a Disadvantage When Seeking Grant Funding?
Authors: Lall Saurabh A. , Chen Li‐Wei , Davidson Abigayle
Published: June 2019

Donor agencies and foundations use grants to stimulate entrepreneurial growth in developing countries. However, some practitioners have asked whether these grants tend to flow to expatriate entrepreneurs with ties to developed countries (where most grants originate), rather than to local entrepreneurs. This article tackles this question using a data set of 3,434 nascent ventures from 92 developing countries. The authors find that ventures with ties to a developed country are significantly more likely to raise grant financing and in more substantial amounts. Ventures with a founder born in a developed country are the most likely to receive grants, with a weaker effect when considering prior work experience in a developed country. This “expat gap” cannot be explained by differences in education level, prior experience, or ties to other developing countries. Donors seeking to support local entrepreneurs in developing countries should consider ways to make their recruitment and selection processes more equitable.
Women’s Empowerment and Child Malnutrition: The Case of Mozambique
Authors: Deutsch Joseph , Silber Jacques
Published: June 2019

Using data from the 2011 Demographic and Health Survey in Mozambique this paper checks whether women empowerment has an impact on the nutritional status of children. We evaluate the degree of empowerment of women via multidimensional approaches, making a distinction between five domains: decision making, use of violence by husband/partner, attitude of the woman towards this use of violence, available information, material resources. Each domain includes several questions reflecting different aspects of empowerment. For each domain of empowerment, three different methods of aggregation are used: correspondence analysis, the so‐called Alkire and Foster methodology and the “fuzzy sets” approach. The impact of women empowerment on the nutritional status of children is analyzed via the MIMIC approach. No clear‐cut conclusion concerning the possible impact of women’s empowerment on the nutritional status of children could be drawn. But, ceteris paribus, the material wealth of the household, the educational level of the mother and her BMI are positively correlated with the nutritional status of children which is also higher when the child is female. Finally, there are important differences in the nutritional status of children between the various regions of Mozambique and this nutritional status is in most regions lower in rural areas.
Introduction to Special Issue on: ‘Inequalities in the Least Developed Countries – Some Lessons from Africa’
Authors: Gradín Carlos , Tarp Finn
Published: June 2019

This special issue comprises six papers analysing different dimensions of inequalities in African countries. Three papers deal with the trend in inequality in consumption in Mozambique, with multidimensional poverty in four sub‐Saharan countries, and with the relationship between living conditions and subjective well‐being in African countries. The other three are focused on gender issues and are focused on Mozambique, dealing with gender inequalities in the access to contract farming arrangements as well as to employment out of subsistence agriculture, or with the effect of women’s empowerment on children’s health. This introduction provides a short overview of how they contribute to a better understanding of inequalities in low‐income countries.
Suicide and Types of Agriculture: A Time‐Series Analysis in Japan
Authors: Kanamori Mariko , Kondo Naoki
Published: June 2019

Objective

In recent years, rural areas have reported higher suicide rates than urban areas worldwide. Although agricultural activity is a key characteristic of many rural areas, rurality may also have heterogeneous qualities based on the type of agriculture pursued. However, to date, no study has examined potential linkages between suicide rate and types of agriculture.

Method

In this study, we used 1983–2007 annual time‐series data of the standardized mortality ratio (SMR) of suicide and product‐specific agricultural outputs in Japanese municipalities to shed light on this phenomenon. We conducted a multilevel linear regression analysis, taking into account a hierarchical structure of the time‐series data, limiting our analysis to municipalities where agricultural land use was high.

Results

Our multilevel analysis showed that the animal husbandry output was positively associated with suicideSMRin both women and men, with a stronger relationship among women, whereas no association was observed in agricultural crop output. Temporal analysis showed that the association could be observed consistently throughout the period between 1983 and 2007.

Conclusions

This study raises the possibility that the industrial and cultural characteristics of communities that rely on animal husbandry may be associated with an increased risk of suicide.
Retrospective evaluation of the association between admission blood glucose and l‐lactate concentrations in ponies and horses with gastrointestinal disease (2008‐2016): 545 cases
Authors: Dunkel Bettina , Mason Charlotte Jane , Chang Yu‐Mei
Published: June 2019

Objectives

A recent study described increased l‐lactate concentrations in ponies with gastrointestinal disease compared to horses, but blood glucose (BG) concentrations were not considered. The study tested the hypothesis that BG and l‐lactate concentrations are correlated in horses and ponies with gastrointestinal disease and that BG concentrations, not equid type (pony vs horse), are an independent predictor of L‐lactate concentrations. It was further hypothesized that equid type was an independent predictor of BG concentrations.

Design

Retrospective study 2008–2016.

Setting

University teaching hospital.

Animals

Admission data from 545 animals (384 horses and 161 ponies) with gastrointestinal disease.

Interventions

None.

Measurements and Main Results

Data collected included signalment, clinicopathological findings on admission, and nature and location of the gastrointestinal lesion (strangulating vs non‐strangulating and large vs small intestinal lesion). The association between admission blood l‐lactate concentrations, equid type (pony or horse) and BG concentrations was investigated in a multivariable model. Admission l‐lactate and BG concentrations were strongly correlated (n = 522; r = 0.63; P < 0.001). Ponies had significantly higher l‐lactate (2.7 mmol/L (0.5–18.0 mmol/L) vs 1.4 mmol/L (0.3–19 mmol/L); P < 0.001) and BG concentrations than horses (8.4 mmol/L (4.2–24.4 mmol/L); 151 mg/dL (76–439 mg/dL) vs 6.9 mmol/L (3.4–26.8 mmol/L); 124 mg/dL (61–482 mg/dL); P < 0.001). In the multivariable analysis, l‐lactate concentrations were significantly and positively associated with admission BG concentrations in all animals and also with equid type. For each millimole per liter (18 mg/dL) increase in BG, l‐lactate concentrations increased by 7.9% (5.9, 9.9); P < 0.001. In comparison to ponies, l‐lactate concentrations were decreased by 27.7% (37.4, 16.5); P < 0.001 in horses. Admission BG concentrations were significantly and positively associated with l‐lactate concentrations in all animals. For each millimole per liter increase in l‐lactate concentration, BG concentration increased by 6.2% (4.7, 7.6; P < 0.001). Admission BG concentrations were not associated with equid type.

Conclusion

Admission BG concentrations and equid type are independent predictors of blood l‐lactate concentrations in equids with gastrointestinal disease, but their relationship requires further investigation.
Effect of intra‐abdominal hypertension on plasma exogenous creatinine clearance in conscious and anesthetized dogs
Authors: Jang Min , Son Won‐Gyun , Jo Sang‐Min , Kim Hyunseok , Shin Chi Won , Lee Inhyung
Published: June 2019

Objective

To evaluate the effect of intra‐abdominal pressure (IAP) on plasma exogenous creatinine clearance in both conscious and anesthetized dog models using a balloon technique to generate intra‐abdominal hypertension.

Design

Prospective, cross‐over, experimental study.

Setting

University‐based small animal research facility.

Animals

Six healthy male Beagle dogs.

Interventions

A balloon device comprising a Foley urinary catheter and latex balloon was placed in the intra‐abdominal cavity. Plasma exogenous creatinine clearance was compared after intravenous administration of exogenous creatinine solution at 80 mg/kg under 4 different treatment conditions as follows: control and IAP levels of 25 mm Hg in conscious dogs and control and IAP levels of 25 mm Hg in anesthetized dogs (CC, C25, AC, and A25, respectively). Samples were obtained before (T0) and 10, 20, 30, 60, 90, 120, 240, 360, 480, and 600 min after administration of creatinine in all treatment groups.

Measurements and main results

There were no significant differences in plasma creatinine concentration for CC, AC, and C25 during the treatment period. However, in the A25 treatment condition, the plasma creatinine concentration increased significantly at 10, 20, 30, 60, 90, and 120 min after administration of creatinine (P < 0.05). Plasma creatinine clearances were 5.0 ± 0.5, 4.7 ± 1.2, 5.5 ± 0.9, and 2.5 ± 0.5 mL/kg/min for 600 min (CC, AC, C25, and A25, respectively). In the A25 treatment condition, the plasma exogenous creatinine clearance decreased significantly to 50%, 47%, and 55% of that under control conditions (CC, AC, and C25, respectively). After decompression of the abdomen, plasma creatinine concentrations declined rapidly and returned to basal concentrations.

Conclusions

Intra‐abdominal hypertension under general anesthesia could cause renal hypoperfusion. Timely decompression may improve the outcome of acutely increased IAP when surgery and/or general anesthesia is required in canine patients.
Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts
Authors: Wang Lianguo , Morotti Stefano , Tapa Srinivas , Francis Stuart Samantha D. , Jiang Yanyan , Wang Zhen , Myles Rachel C. , Brack Kieran E. , Ng G. André , Bers Donald M. , Grandi Eleonora , Ripplinger Crystal M.
Published: June 2019

Key points

Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.

Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.

In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.

Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.

Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses.

Sympathetic activation of the heart results in positive chronotropy and inotropy, which together rapidly increase cardiac output. The precise mechanisms that produce the electrophysiological and Ca2+ handling changes underlying chronotropic and inotropic responses have been studied in detail in isolated cardiac myocytes. However, few studies have examined the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (APs) and intracellular Ca2+ transients (CaTs) in the intact heart. Here, we performed bilateral sympathetic nerve stimulation (SNS) in fully innervated, Langendorff‐perfused rabbit and mouse hearts. Dual optical mapping with voltage‐ and Ca2+‐sensitive dyes allowed for analysis of spatio‐temporal AP and CaT dynamics. The rabbit heart responded to SNS with a monotonic increase in heart rate (HR), monotonic decreases in AP and CaT duration (APD, CaTD), and a monotonic increase in CaT amplitude. The mouse heart had similar HR and CaT responses; however, a pronounced biphasic APD response occurred, with initial prolongation (50.9 ± 5.1 ms at t = 0 s vs. 60.6 ± 4.1 ms at t = 15 s, P < 0.05) followed by shortening (46.5 ± 9.1 ms at t = 60 s, P = NS vs. t = 0). We determined the biphasic APD response in mouse was partly due to dynamic changes in HR during SNS and was exacerbated by β‐adrenergic activation. Simulations with species‐specific cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid CaT responses, suggesting more rapid increases in contractility; conversely, the rabbit heart requires APD shortening to produce optimal inotropic responses. Thus, while the cardiac fight‐or‐flight response is highly conserved between species, the underlying mechanisms orchestrating these effects differ significantly.
Endocytic recycling of Na+–K+–Cl− cotransporter type 2: importance of exon 4
Authors: Marcoux Andrée‐Anne , Slimani Samira , Tremblay Laurence E. , Frenette‐Cotton Rachelle , Garneau Alexandre P. , Isenring Paul
Published: June 2019

Key points

Na+–K+–Cl− cotransporter type 2 (NKCC2) is a 27‐exon membrane protein that is expressed in the thick ascending limb (TAL) of Henle where it is involved in reabsorption of the ultrafiltered NaCl load.

It comes as three splice variants that are identical to each other except for the residue composition of exon 4 and that differ in their transport characteristics, functional roles and distributions along the TAL.

In this report, it is shown that the variants also differ in their trafficking properties and that two residues in exon 4 play a key role in this regard. One of these residues was also shown to sustain carrier internalization.

Through these results, a novel function for the alternatively spliced exon of NKCC2 has been identified and a domain that is involved in carrier trafficking has been uncovered for the first time in a cation–Cl− cotransporter family member.

Na+–K+–Cl− cotransporter type 2 (NKCC2) is a 12‐transmembrane (TM) domain cell surface glycoprotein that is expressed in the thick ascending limb (TAL) of Henle and stimulated during cell shrinkage. It comes as three splice variants (A, B and F) that are identical to each other except for TM2 and the following connecting segment (CS2). Yet, these variants do not share the same localization, transport characteristics and physiological roles along the TAL. We have recently found that while cell shrinkage could exert its activating effect by increasing NKCC2 expression at the cell surface, the variants also responded differentially to this stimulus. In the current work, a mutagenic approach was exploited to determine whether CS2 could play a role in carrier trafficking and identify the residues potentially involved. We found that when the residue of position 238 in NKCC2A (F) and NKCC2B (Y) was replaced by the corresponding residue in NKCC2F (V), carrier activity increased by over 3‐fold and endocytosis decreased concomitantly. We also found that when the residue of position 230 in NKCC2F (M) was replaced by the one in NKCC2B (T), carrier activity and affinity for ions both increased substantially whereas expression at the membrane decreased. Taken together, these results suggest that CS2 is involved in carrier trafficking and that two of its residues, those of positions 238 and 230, are part of an internalization motif. They also indicate that the divergent residue of position 230 plays the dual role of specifying ion affinity and sustaining carrier internalization.
H‐reflex conditioning during locomotion in people with spinal cord injury
Authors: Thompson Aiko K. , Wolpaw Jonathan R.
Published: June 2019

Key points

In people or animals with incomplete spinal cord injury (SCI), changing a spinal reflex through an operant conditioning protocol can improve locomotion.

All previous studies conditioned the reflex during steady‐state maintenance of a specific posture. By contrast, the present study down‐conditioned the reflex during the swing‐phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The aim was to modify the functioning of the reflex in a specific phase of a dynamic movement.

This novel swing‐phase conditioning protocol decreased the reflex much faster and farther than did the steady‐state protocol in people or animals with or without SCI, and it also improved locomotion.

The reflex decrease persisted for at least 6 months after conditioning ended.

The results suggest that conditioning reflex function in a specific phase of a dynamic movement offers a new approach to enhancing and/or accelerating recovery after SCI or in other disorders.

In animals and people with incomplete spinal cord injury, appropriate operant conditioning of a spinal reflex can improve impaired locomotion. In all previous conditioning studies, the reflex was conditioned during steady‐state maintenance of a stable posture; this steady‐state protocol aimed to change the excitability of the targeted reflex pathway; reflex size gradually changed over 8–10 weeks. The present study introduces a new protocol, comprising a dynamic protocol that aims to change the functioning of the reflex pathway during a specific phase of a complex movement. Specifically, we down‐conditioned the soleus H‐reflex during the swing‐phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The swing‐phase H‐reflex, which is absent or very small in neurologically normal individuals, is abnormally large in this patient population. The results were clear. With swing‐phase down‐conditioning, the H‐reflex decreased much faster and farther than did the H‐reflex in all previous animal or human studies with the steady‐state protocol, and the decrease persisted for at least 6 months after conditioning ended. The H‐reflex decrease was accompanied by improvements in walking speed and in the modulation of locomotor electromyograph activity in proximal and distal muscles of both legs. These results provide new insight into the factors controlling spinal reflex conditioning; they suggest that the conditioning protocols targeting reflex function in a specific movement phase provide a promising new opportunity to enhance functional recovery after SCI or in other disorders.
Two new species and an additional record of eriophyoids (Acari: Trombidiformes: Eriophyidae) from semi-arid and arid environments in East Iran
Authors: Honarmand Arash , Sadeghi Namaghi Hussein , De Lillo Enrico
Published: June 2019

Two new species and an additional record of eriophyid mites from semi-arid and arid environments in East Iran are reported. Aculops ammodendris sp. nov. from Ammodendron persicum Bunge ex Boiss. (Leguminosae) and Aceria launaeae sp. nov. from Launaea acanthodes (Boiss.) Kuntze (Asteraceae) are described and illustrated. No symptoms were observed on the infested host plants. These two new species are the first eriophyid mites on plant species within the genera Ammodendron and Launaea. Geographical distribution of Aceria angustifoliae Denizhan, Monfreda, de Lillo & Çobanoglu, 2008, extended also into the currently studied Iranian area in addition to a previous record from Turkey and Northern Khorasan.
Contribution of the Greenland Ice Sheet to sea level over the next millennium
Authors: Aschwanden Andy , Fahnestock Mark A. , Truffer Martin , Brinkerhoff Douglas J. , Hock Regine , Khroulev Constantine , Mottram Ruth , Khan S. Abbas
Published: June 2019

Simulations show that the Greenland Ice Sheet could disappear within a millennium if greenhouse gas emissions continue unabated.
Single-cell imaging and characterization of
Escherichia coli
persister cells to ofloxacin in exponential cultures
Authors: Goormaghtigh Frédéric , Van Melderen Laurence
Published: June 2019

Persister cells to ofloxacin are not necessarily slow growers and do endure DNA damages, similar to their sensitive siblings.
Sortilin gates neurotensin and BDNF signaling to control peripheral neuropathic pain
Authors: Richner Mette , Pallesen Lone T. , Ulrichsen Maj , Poulsen Ebbe T. , Holm Thomas H. , Login Hande , Castonguay Annie , Lorenzo Louis-Etienne , Gonçalves Nádia P. , Andersen Olav M. , Lykke-Hartmann Karin , Enghild Jan J. , Rønn Lars C. B. , Malik Ibrahim J. , De Koninck Yves , Bjerrum Ole J. , Vægter Christian B. , Nykjær Anders
Published: June 2019

Blocking of sortilin ligand binding prevents neuropathic pain by inhibiting BDNF-induced spinal KCC2 down-regulation.
Archaea dominate oxic subseafloor communities over multimillion-year time scales
Authors: Vuillemin Aurèle , Wankel Scott D. , Coskun Ömer K. , Magritsch Tobias , Vargas Sergio , Estes Emily R. , Spivack Arthur J. , Smith David C. , Pockalny Robert , Murray Richard W. , D’Hondt Steven , Orsi William D.
Published: June 2019

Archaea have dominated oxic subseafloor communities for millions of years by minimizing energy loss.
Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins
Authors: Yen Tien-Jui , Lolicato Marco , Thomas-Tran Rhiannon , Du Bois J. , Minor Daniel L.
Published: June 2019

Bullfrog saxiphilin:STX complex defines a toxin “molecular sponge” blueprint for STX recognition and toxin resistance.
Intelligent magnetic manipulation for gastrointestinal ultrasound
Authors: Norton Joseph C. , Slawinski Piotr R. , Lay Holly S. , Martin James W. , Cox Benjamin F. , Cummins Gerard , Desmulliez Marc P.Y. , Clutton Richard E. , Obstein Keith L. , Cochran Sandy , Valdastri Pietro
Published: June 2019

A capsule robot uses magnetic control and microultrasound feedback for in situ autonomous positioning and diagnostics of microanatomy.
Noninvasive neuroimaging enhances continuous neural tracking for robotic device control
Authors: Edelman B. J. , Meng J. , Suma D. , Zurn C. , Nagarajan E. , Baxter B. S. , Cline C. C. , He B.
Published: June 2019

Noninvasive neuroimaging and increased user engagement improve EEG-based neural decoding and facilitate real-time 2D robotic device control.
Targeting pancreatic islet PTP1B improves islet graft revascularization and transplant outcomes
Authors: Figueiredo Hugo , Figueroa Ana Lucia C. , Garcia Ainhoa , Fernandez-Ruiz Rebeca , Broca Christophe , Wojtusciszyn Anne , Malpique Rita , Gasa Rosa , Gomis Ramon
Published: June 2019

Inhibition of tyrosine phosphatase PTP1B in mouse and human islets promotes islet revascularization and improves graft survival and function.
Comment on “An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness”
Authors: Penno Carlos A. , Wack Nathalie , Laguerre Claire , Hasler Franziska , Numao Shin , Röhn Till A.
Published: June 2019

Increased airway hyperresponsiveness and epithelial remodeling in asthmatic LTA
4
H-KO mice may be mediated by CysLTs rather than elevated tripeptide PGP.
Targetable genetic alterations of
TCF4
(
E2-2
) drive immunoglobulin expression in diffuse large B cell lymphoma
Authors: Jain Neeraj , Hartert Keenan , Tadros Saber , Fiskus Warren , Havranek Ondrej , Ma Man Chun John , Bouska Alyssa , Heavican Tayla , Kumar Dhiraj , Deng Qing , Moore Dalia , Pak Christine , Liu Chih Long , Gentles Andrew J. , Hartmann Elena , Kridel Robert , Smedby Karin Ekstrom , Juliusson Gunnar , Rosenquist Richard , Gascoyne Randy D. , Rosenwald Andreas , Giancotti Filippo , Neelapu Sattva S. , Westin Jason , Vose Julie M. , Lunning Matthew A. , Greiner Timothy , Rodig Scott , Iqbal Javeed , Alizadeh Ash A. , Davis R. Eric , Bhalla Kapil , Green Michael R.
Published: June 2019

Frequently observed DNA copy number gains of
TCF4
in ABC-like DLBCL promote immunoglobulin expression and are targetable by BET inhibition.
Epigenetic activation and memory at a
TGFB2
enhancer in systemic sclerosis
Authors: Shin Joseph Yusup , Beckett James Daniel , Bagirzadeh Rustam , Creamer Tyler J. , Shah Ami A. , McMahan Zsuzsanna , Paik Julie J. , Sampedro Margaret M. , MacFarlane Elena G. , Beer Michael A. , Warren Daniel , Wigley Fredrick M. , Dietz Harry C.
Published: June 2019

NF-κB and BRD4 epigenetically activate a
TGFB2
enhancer to lock sclerotic patient fibroblasts into a profibrotic synthetic state.
Vaccines and global health: In search of a sustainable model for vaccine development and delivery
Authors: Rappuoli Rino , Black Steven , Bloom David E.
Published: June 2019

Sustainable development of vaccines for global health requires considerable investment and close collaborations between public and private sectors.
Coaxing cancer control by modulating COX-2
Authors: Kulkarni Rajan P.
Published: June 2019

Mouse models of pancreatic ductal adenocarcinoma respond to immunotherapy when given in combination with the cyclooxygenase-2 inhibitor celecoxib.
Biological Impact of a Large-Scale Genomic Inversion That Grossly Disrupts the Relative Positions of the Origin and Terminus Loci of the Streptococcus pyogenes Chromosome
Authors: Savic Dragutin J. , Nguyen Scott V. , McCullor Kimberly , McShan W. Michael
Published: June 2019

Based on our previous work, we created to our knowledge the largest asymmetric inversion, covering 43.5% of the
S. pyogenes
genome. In spite of a drastic replacement of origin of replication and the unbalanced size of replichores (1.4 Mb versus 0.41 Mb), the invertant, when not challenged with its progenitor, showed impressive vitality for growth
in vitro
and in pathogenesis assays. The mutant supports the existing idea that slightly deleterious mutations can provide the setting for secondary adaptive changes. Furthermore, comparative analysis of the mutant with previously published data strongly indicates that even large genomic rearrangements survive provided that the integrity of the
oriC
and the chromosome partition cluster is preserved.
Guanine Quadruplex DNA Regulates Gamma Radiation Response of Genome Functions in the Radioresistant Bacterium
Deinococcus radiodurans
Authors: Mishra Shruti , Chaudhary Reema , Singh Sudhir , Kota Swathi , Misra Hari S.
Published: June 2019

Deinococcus radiodurans
can recover from extensive DNA damage caused by many genotoxic agents. It lacks LexA/RecA-mediated canonical SOS response. Therefore, the molecular mechanisms underlying the regulation of DNA damage response would be worth investigating in this bacterium.
D. radiodurans
genome is GC-rich and contains numerous islands of putative guanine quadruplex (G4) DNA structure-forming motifs. Here, we showed that
in vivo
stabilization of G4 DNA structures can impair DNA damage response processes in
D. radiodurans
. Essential cellular processes such as transcription, DNA synthesis, and protein translation, which are also an integral part of the double-strand DNA break repair pathway, are affected by the arrest of G4 DNA structure dynamics. Thus, the role of DNA secondary structures in DNA damage response and radioresistance is demonstrated.
Simian-Human Immunodeficiency Virus SHIV.CH505 Infection of Rhesus Macaques Results in Persistent Viral Replication and Induces Intestinal Immunopathology
Authors: Bar Katharine J. , Coronado Ernesto , Hensley-McBain Tiffany , O’Connor Megan A. , Osborn Jessica M. , Miller Charlene , Gott Toni M. , Wangari Solomon , Iwayama Naoto , Ahrens Chul Y. , Smedley Jeremy , Moats Cassie , Lynch Rebecca M. , Haddad Elias K. , Haigwood Nancy L. , Fuller Deborah H. , Shaw George M. , Klatt Nichole R. , Manuzak Jennifer A.
Published: June 2019

The development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing for
in vivo
testing of novel treatments. However, many of the currently available SHIVs have distinct drawbacks and are unable to fully reflect the features characteristic of primary SIV and HIV strains. Here, we utilize rhesus macaques to define the immunopathogenesis of the recently developed SHIV.CH505, which was designed without many of the limitations of previous SHIVs. We observed that infection with SHIV.CH505 leads to peripheral viral kinetics and mucosal immunopathogenesis comparable with those caused by pathogenic SIV and HIV. Overall, these data provide evidence of the value of SHIV.CH505 as an effective model of SIV/HIV infection and an important tool that can be used in future studies, including preclinical testing of new therapies or prevention strategies.
Genomics of the Pathogenic Clostridia
Authors: Moore Robert J. , Lacey Jake A.
Published: June 2019

Whole-genome sequences are now available for all the clinically important clostridia and many of the lesser or opportunistically pathogenic clostridia. The complex clade structures of
C. difficile
,
C. perfringens
, and the species that produce botulinum toxins have been delineated by whole-genome sequence analysis. The true clostridia of cluster I show relatively low levels of gross genomic rearrangements within species, in contrast to the species of cluster XI, notably
C. difficile
, which have been found to have very plastic genomes with significant levels of chromosomal rearrangement. Throughout the clostridial phylotypes, a large proportion of the strain diversity is driven by the acquisition and loss of mobile elements, including phages, plasmids, insertion sequences, and transposons. Genomic analysis has been used to investigate the diversity and spread of
C. difficile
within hospital settings, the zoonotic transfer of isolates, and the emergence, origins, and geographic spread of epidemic ribotypes. In
C. perfringens
the clades defined by chromosomal sequence analysis show no indications of clustering based on host species or geographical location. Whole-genome sequence analysis helps to define the different survival and pathogenesis strategies that the clostridia use. Some, such as
C. botulinum
, produce toxins which rapidly act to kill the host, whereas others, such as
C. perfringens
and
C. difficile
, produce less lethal toxins which can damage tissue but do not rapidly kill the host. The genomes provide a resource that can be mined to identify potential vaccine antigens and targets for other forms of therapeutic intervention.
Discovery and Characterization of Bacteriophage LuckyBarnes
Authors: Underwood Savannah L. , Foto Amanda , Ray Amanda F. , Nelms Alexander E. , Kennedy Keyshawn L. , Hartley Shelby G. , Ryals Logan M. , Gurung Chandan , D’Angelo William A. , Pope Welkin H. , Mavrodi Dmitri V.
Published: June 2019

Here, we report the genome sequence of LuckyBarnes, a newly isolated singleton siphovirus that infects
Brevibacterium iodinum
ATCC 15728 and has a 50,774-bp genome with 67 predicted genes.
Complete Sequence and Annotation of the Mycoplasma phocicerebrale Strain 1049
T
Genome
Authors: Frasca Salvatore , Castellanos Gell Jessy , Kutish Gerald F. , Michaels Dina L. , Brown Daniel R.
Published: June 2019

The
Mycoplasma phocicerebrale
genome was analyzed to better understand this opportunistic pathogen. Amplification with ϕ29 polymerase was used to generate enough genomic DNA for large-insert library construction. Like other mycoplasmas from seals,
M. phocicerebrale
encodes an immunosuppressor that may predispose susceptibility to infection or influence intercurrent diseases of affected hosts.
Draft Genome Sequence of Strain LSUCC0057, a Member of the SAR92 Clade of
Gammaproteobacteria
Authors: Lanclos V. Celeste , Henson Michael W. , Doiron Chase , Thrash J. Cameron
Published: June 2019

We present the draft genome sequence of strain LSUCC0057, a member of the SAR92 clade of
Gammaproteobacteria
, isolated from coastal waters near Buras, LA. The genome contains proteorhodopsin and indicates the potential for aerobic heterotrophy, assimilatory sulfate reduction, and carotenoid biosynthesis.
Erosion rates and patterns in a transient landscape, Grand Staircase, southern Utah, USA
Authors: Riley Kerry E. , Rittenour Tammy M. , Pederson Joel L. , Belmont Patrick
Published: June 2019

Cosmogenic 10Be concentrations in alluvial sediment are widely used to infer long-term, catchment-averaged erosion rates based on the assumption that the landscape is in mass-flux steady state. However, many landscapes are out of equilibrium over millennial time scales due to tectonic and climatic forcing. The Grand Staircase of the Colorado Plateau (North America) is a transient landscape, adjusting to base-level fall from the carving of the Grand Canyon, and is characterized by cliff-bench topography caused by differential erosion of lithologic units. The 10Be concentrations from 52 alluvial and colluvial samples, collected in nested fashion from five catchments, produced inferred erosion rates ranging from 20 to >3500 m/m.y. (or mm/k.y.). We attribute this high variance in part to lithologic-controlled steepness and hotspots of erosion related to cliff retreat along the White Cliffs (escarpment near Mt. Carmel Junction, Utah), as well as headward drainage expansion along the uppermost Pink Cliffs (escarpment within Bryce Canyon National Park). Results from the downslope Vermillion Cliffs (near Kanab) indicate lower erosion rates despite similar slope and rock types, suggesting knick-zone migration has passed that lower region of our study area. The 10Be concentrations measured along trunk streams systematically match local, subcatchment erosion rates, with muted influence from upstream sediment sources. This is consistent with intermittent sediment conveyance between cliff and bench terrain, with sediment storage and localized release associated with ephemeral arroyo systems in the region. Therefore, while detrital cosmogenic nuclide records in transient landscapes may not directly reflect upstream catchment-averaged erosion rates, 10Be inventories can provide insight into unsteady upslope-directed erosion and downslope-directed sediment conveyance in these dynamic landscapes.
Eosinophilic granulomatosis with polyangiitis in a Nigerian woman
Authors: Ekeigwe Ngozi Lina , Adelowo Olufemi , Anaba Ehiaghe Lonia , Olaosebikan Hakeem
Published: June 2019

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss Syndrome, is a systemic autoimmune disease that is usually associated with asthma and eosinophilia. It is a rare condition associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of a 52-year-old Nigerian woman who presented with bilateral leg swelling with multiple ulcers, background history of allergic rhinitis and chronic sinusitis since adolescence. There were also associated symptoms of peripheral neuropathy, weight loss, peripheral blood eosinophilia and positive perinuclear ANCA and she was previously managed for rheumatoid arthritis and asthma. She fulfilled the American College of Rheumatology criteria for EGPA and was treated with glucocorticoids and methotrexate which led to significant improvement of her symptoms.