bluuebunny/crossref_metadata_2025 huggingface dataset:
UFMTrack: Under-Flow Migration Tracker enabling analysis of the entire multi-step immune cell extravasation cascade across the blood-brain barrier in microfluidic devices
Authors: Vladymyrov Mykhailo , Marchetti Luca , Aydin Sidar , Soldati Sasha , Mossu Adrien , Pal Arindam , Gueissaz Laurent , Ariga Akitaka , Engelhardt Britta
Published: May 2024

The endothelial blood-brain barrier (BBB) strictly controls immune cell trafficking into the central nervous system (CNS). In neuroinflammatory diseases such as multiple sclerosis, this tight control is, however, disturbed, leading to immune cell infiltration into the CNS. The development of in vitro models of the BBB combined with microfluidic devices has advanced our understanding of the cellular and molecular mechanisms mediating the multi-step T-cell extravasation across the BBB. A major bottleneck of these in vitro studies is the absence of a robust and automated pipeline suitable for analyzing and quantifying the sequential interaction steps of different immune cell subsets with the BBB under physiological flow in vitro.Here we present the Under-Flow Migration Tracker (
UFM
Track) framework for studying immune cell interactions with endothelial monolayers under physiological flow. We then showcase a pipeline built based on it to study the entire multi-step extravasation cascade of immune cells across brain microvascular endothelial cells under physiological flow in vitro.
UFM
Track achieves 90% track reconstruction efficiency and allows for scaling due to the reduction of the analysis cost and by eliminating experimenter bias. This allowed for an in-depth analysis of all behavioral regimes involved in the multi-step immune cell extravasation cascade. The study summarizes how
UFM
Track can be employed to delineate the interactions of CD4
+
and CD8
+
T cells with the BBB under physiological flow. We also demonstrate its applicability to the other BBB models, showcasing broader applicability of the developed framework to a range of immune cell-endothelial monolayer interaction studies. The
UFM
Track framework along with the generated datasets is publicly available in the corresponding repositories.
circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA
Authors: Hauge Okholm Trine Line , Kamstrup Andreas Bjerregaard , Nielsen Morten Muhlig , Hollensen Anne Kruse , Graversgaard Mette Laugesen , Sørensen Matilde Helbo , Kristensen Lasse Sommer , Vang Søren , Park Samuel S. , Yeo Gene W. , Dyrskjøt Lars , Kjems Jørgen , Pedersen Jakob Skou , Damgaard Christian Kroun
Published: May 2024

Circular RNAs (circRNAs) represent a class of widespread endogenous RNAs that regulate gene expression and thereby influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Specifically, we use temporal depletion of circHIPK3 or specific RNA binding proteins (RBPs) and identify several perturbed genes by RNA sequencing analyses. Using expression-coupled motif analyses of mRNA expression data from various knockdown experiments, we identify an 11-mer motif within circHIPK3, which is also enriched in genes that become downregulated upon circHIPK3 depletion. By mining eCLIP datasets, we find that the 11-mer motif constitutes a strong binding site for IGF2BP2 and validate this circHIPK3-IGF2BP2 interaction experimentally using RNA-immunoprecipitation and competition assays in bladder cancer cell lines. Our results suggest that circHIPK3 and IGF2BP2 mRNA targets compete for binding. Since the identified 11-mer motif found in circHIPK3 is enriched in upregulated genes following IGF2BP2 knockdown, and since IGF2BP2 depletion conversely globally antagonizes the effect of circHIPK3 knockdown on target genes, our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the
STAT3
mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-
STAT3
mRNA binding and thereby
STAT3
mRNA levels. However, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Finally, we show that circHIPK3 expression correlates with overall survival of patients with bladder cancer. Our results are consistent with a model where relatively few cellular circHIPK3 molecules function as inducers of IGF2BP2 condensation thereby regulating STAT3 and other key factors for cell proliferation and potentially cancer progression.
Alasemenia, the earliest ovule with three wings and without cupule
Authors: Wang Deming , Yang Jiangnan , Liu Le , Zhou Yi , Xu Peng , Qin Min , Huang Pu
Published: May 2024

The ovules or seeds (fertilized ovules) with wings are widespread and especially important for wind dispersal. However, the earliest ovules in the Famennian of the Late Devonian are rarely known about the dispersal syndrome and usually surrounded by a cupule. From Xinhang, Anhui, China, we report a new taxon of Famennian ovules,
Alasemenia tria
gen. et sp. nov. Each ovule possesses three integumentary wings evidently extending outwards, folding inwards along abaxial side and enclosing most part of nucellus. The ovule is borne terminally on smooth dichotomous branches and lacks a cupule.
Alasemenia
suggests that the integuments of the earliest ovules without a cupule evolved functions in wind dispersal and probable photosynthetic nutrition. It indicates that the seed wing originated earlier than other wind dispersal mechanisms such as seed plume and pappus, and that three- or four-winged seeds were followed by seeds with less wings. Mathematical analysis shows that three-winged seeds are more adapted to wind dispersal than seeds with one, two or four wings under the same condition.
Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair
Authors: Phelps Patricia E , Ha Sung Min , Khankan Rana R , Mekonnen Mahlet A , Juarez Giovanni , Ingraham Dixie Kaitlin L , Chen Yen-Wei , Yang Xia
Published: May 2024

Olfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair and axonal regeneration.
Olfactory ensheathing cells are hybrid glial cells that promote neural repair
Authors: Phelps Patricia E. , Ha Sung Min , Khankan Rana R. , Mekonnen Mahlet A. , Juarez Giovanni , Ingraham Dixie Kaitlin L. , Chen Yen-Wei , Yang Xia
Published: May 2024

Olfactory ensheathing cells (OECs) are unique glial cells found in both the central and peripheral nervous systems where they support the continuous axonal outgrowth of immature olfactory sensory neurons to their targets. Here we show that following severe spinal cord injury, olfactory bulb-derived OECs transplanted near the injury site modify the normally inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion center. To understand the mechanisms underlying the reparative properties of such transplanted OECs, we used single-cell RNA-sequencing to study their gene expression programs. Our analyses revealed five diverse subtypes of OECs, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration and repair, secreted molecules, or microglia-like functions. As expected, we found substantial overlap of OEC genes with those of Schwann cells, but also with astrocytes, oligodendrocytes and microglia. We confirmed established markers on cultured OECs, and then localized select top genes of OEC subtypes in rat olfactory bulb tissue. In addition, we present evidence that OECs secrete both Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that adult OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate diverse functions related to wound healing, injury repair and axonal regeneration.
Mapping spatial patterns to energetic benefits in groups of flow-coupled swimmers
Authors: Heydari Sina , Hang Haotian , Kanso Eva
Published: May 2024

The coordinated motion of animal groups through fluids is thought to reduce the cost of locomotion to individuals in the group. However, the connection between the spatial patterns observed in collectively moving animals and the energetic benefits at each position within the group remains unclear. To address this knowledge gap, we study the spontaneous emergence of cohesive formations in groups of fish, modeled as flapping foils, all heading in the same direction. We show in pairwise formations and with increasing group size that (1) in side-by-side arrangements, the reciprocal nature of flow coupling results in an equal distribution of energy requirements among all members, with reduction in cost of locomotion for swimmers flapping inphase but an increase in cost for swimmers flapping antiphase, and (2) in inline arrangements, flow coupling is non-reciprocal for all flapping phase, with energetic savings in favor of trailing swimmers, but only up to a finite number of swimmers, beyond which school cohesion and energetic benefits are lost at once. We explain these findings mechanistically and we provide efficient diagnostic tools for identifying locations in the wake of single and multiple swimmers that offer opportunities for hydrodynamic benefits to aspiring followers. Our results imply a connection between the resources generated by flow physics and social traits that influence greedy and cooperative group behavior.
A microglia clonal inflammatory disorder in Alzheimer’s Disease
Authors: Vicario Rocio , Fragkogianni Stamatina , Weber Leslie , Lazarov Tomi , Hu Yang , Hayashi Samantha Y. , Craddock Barbara P. , Socci Nicholas D. , Alberdi Araitz , Baako Ann , Ay Oyku , Ogishi Masato , Lopez-Rodrigo Estibaliz , Kappagantula Rajya , Viale Agnes , Iacobuzio-Donahue Christine A. , Zhou Ting , Ransohoff Richard M , Chesworth Richard ,   Netherlands Brain Bank, Abdel-Wahab Omar , Boisson Bertrand , Elemento Olivier , Casanova Jean-Laurent , Miller W. Todd , Geissmann Frederic
Published: May 2024

Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer’s Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both
in vitro
and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in human, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.
One-Sentence Summary:
A subset of Alzheimer Disease patients carry mutant microglia somatic clones which promote neuro-inflammation.
Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells
Authors: Alexander Adriana K. , Rodriguez Karina F. , Chen Yu-Ying , Amato Ciro M. , Estermann Martin A. , Xu Xin , Yao Humphrey Hung-Chang
Published: May 2024

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate.
Fractal cycles of sleep: a new aperiodic activity-based definition of sleep cycles
Authors: Rosenblum Yevgenia , Esfahani Mahdad Jafarzadeh , Adelhöfer Nico , Zerr Paul , Furrer Melanie , Huber Reto , Steiger Axel , Zeising Marcel , Horváth Csenge G. , Schneider Bence , Bódizs Róbert , Dresler Martin
Published: May 2024

Nocturnal human sleep consists of 4 – 6 ninety-minute cycles defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. While sleep cycles are considered fundamental components of sleep, their functional significance largely remains unclear. One of the reasons for a lack of research progress in this field is the absence of a “data-driven” definition of sleep cycles. Here, we proposed to base such a definition on fractal (aperiodic) neural activity, a well-established marker of arousal and sleep stages.We explored temporal dynamics of fractal activity during nocturnal sleep using electroencephalography in 205 healthy adults aged 18 – 75 years. Based on the observed pattern of fractal fluctuations, we introduced a new concept, the “fractal” cycle of sleep, defined as a time interval during which fractal activity descends from its local maximum to its local minimum and then leads back to the next local maximum. Then, we assessed correlations between “fractal” and “classical” (i.e., non-REM – REM) sleep cycle durations. We also studied cycles with skipped REM sleep, i.e., the cycles where the REM phase is replaced by “lightening” of sleep. Finally, we validated the fractal cycle concept in children and adolescents (range: 8 – 17 years, n = 21), the group characterized by deeper sleep and a higher frequency of cycles with skipped REM sleep, as well as in major depressive disorder (n = 111), the condition characterized by altered sleep structure (in addition to its clinical symptoms).We found that “fractal” and “classical” cycle durations (89 ± 34 min
vs.
90 ± 25 min) correlated positively (r = 0.5, p < 0.001). Cycle-to-cycle overnight dynamics showed an inverted U-shape of both fractal and classical cycle durations and a gradual decrease in absolute amplitudes of the fractal descents and ascents from early to late cycles.In adults, the “fractal” cycle duration and participant’s age correlated negatively (r = -0.2, p = 0.006). Children and adolescents had shorter “fractal” cycles compared to young adults (76 ± 34
vs.
94 ± 32 min, p < 0.001). The fractal cycle algorithm detected cycles with skipped REM sleep in 53/55 (96%) cases.Medicated patients with depression showed longer “fractal” cycles compared to their own unmedicated state (107 ± 51 min
vs.
92 ± 38 min, p < 0.001) and age-matched controls (104 ± 49
vs.
88 ± 31 min, p < 0.001).In conclusion, “fractal” cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycling nature. They are useful in healthy, pediatric and clinical populations and should be extensively studied to advance theoretical research on sleep structure.
Contribution of the epididymis beyond fertilization: relevance of CRISP1 and CRISP3 for sperm DNA integrity and early embryo development
Authors: Valeria Sulzyk , Ludmila Curci , González Lucas N , Abril Rebagliati Cid , Mariana Weigel Muñoz , Cuasnicu Patricia S
Published: May 2024

Numerous reports show that the epididymis plays a key role in the acquisition of sperm fertilizing ability but less information exists on its contribution to embryo development. Evidence from our laboratory showed that mammalian CRISP (Cysteine-Rich Secretory Proteins), known to be expressed in the epididymis, to regulate calcium (Ca
2+
) channels and to participate in fertilization, may also be relevant for embryo development. More specifically, we found that males with simultaneous mutations in
Crisp1
and
Crisp3
genes exhibited normal
in vivo
fertilization but impaired embryo development. In the present work, aimed to investigate the mechanisms underlying this reproductive phenotype, we observed that embryo development failure was not due to delayed fertilization as no differences in sperm transport within the female tract nor in
in vivo
fertilization were found shortly after mating. The observation that impaired embryo development was also found in eggs fertilized by epididymal sperm either after uterine insemination or
in vitro
fertilization, revealed that the defects were already present at epididymal level. Of note, eggs fertilized
in vitro
by mutant sperm exhibited impaired meiotic resumption not due to defects in Ca
2+
oscillations during egg activation, prompting us to examine potential sperm DNA defects. Interestingly, higher levels of both DNA fragmentation and intracellular Ca
2+
were observed for mutant than for control epididymal sperm, supporting sperm DNA damage, likely linked to a Ca
2+
dysregulation, as the main responsible for the early development failure of mutant males. Together, our results support the contribution of the epididymis beyond fertilization, identifying CRISP1 and CRISP3 as novel male factors relevant for DNA integrity and early embryo development. Given the existence of human functional homologues of CRISP and the incidence of DNA fragmentation in infertile men, we believe these findings not only provide relevant information on the impact of epididymal factors on embryonic development but will also contribute to a better understanding, diagnosis and treatment of human infertility.
No benefit of higher protein dosing in critically ill patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Qin Yonggen , Huang Jian , Ping Xiaofeng , Zheng Hui , Zhang Kai , Xu Xiaoya , Yu Jiuqing
Published: May 2024

Purpose

The optimal range of protein dosage and effect of high-dose protein on critically ill patients remain controversial. We conducted a meta-analysis to compare higher and lower doses of protein supplementation for nutritional support in critically ill patients.

Methods

We searched the PubMed, Embase, Scopus, and Cochrane Library databases for randomized controlled trials that compared higher (≥1.2 g/kg per day) versus lower (<1.2 g/kg per day) doses of protein supplementation among critically ill adult patients. This search spanned from the inception of relevant databases to November 20, 2023. Our primary endpoint of interest was overall mortality, while secondary endpoints included length of stay in the intensive care unit, length of hospital stay, duration of mechanical ventilation, and incidence of acute kidney injury.

Results

Seventeen studies including 2,965 critically ill patients were included in our meta-analysis. The pooled analyses showed no significant difference in overall mortality (RR 1.03, 95%CI [0.92–1.15], P = 0.65, I2 = 0%), length of intensive care unit stay (MD 0.19, 95%CI [−0.67 to 1.04], P = 0.66, I2 = 25%), length of hospital stay (MD 0.73, 95%CI [−1.59 to 3.04], P = 0.54, I2 = 27%), duration of mechanical ventilation (MD −0.14, 95%CI [−0.83 to 0.54], P = 0.68, I2 = 8%), and incidence of acute kidney injury (RR 1.11, 95%CI [0.87–1.41], P = 0.38, I2 = 0%) between critically ill patients receiving higher or lower doses of protein supplementation.

Conclusions

For critically ill patients, the protein supplementation dose had no significant effect on clinical outcomes, including overall mortality, length of intensive care unit and hospital stay, duration of mechanical ventilation, and incidence of acute kidney injury.
Varietal Evaluation in Sweet Potato Cultivated under Prayagraj Conditions, India
Authors: Ranasingh Nishigandha , Singh Devi , Bahadur Vijay , Verma Riya , Yadav Preksha
Published: May 2024

Sweet potato is regarded as one of the most important food crops mostly grown in sub -Saharan Africa, Pacific islands and parts of Asia. It is mostly grown for human consumptions. It has been domesticated for more than 5000 years in the Latin America and further more cultivated in the developing countries. This research experiment was conducted in the Horticulture research field, at Department of Horticulture under Sam Higginbottom University of Agriculture, Technology and Science, Prayagraj, Uttar Pradesh, India. Five different cultivars of Sweet potato were evaluated by replicating thrice in Randomized block design method during rabi season 2023. Among the growth parameters and yield parameters the character that were observed are like Vines length (cm), Number of leaves per plant, Numbers of vines per plant, Inter-nodal length (cm), Numbers of tubers per plant, Tuber length (cm), Tuber diameter (cm), Tuber weight (g), Tuber yield per plant (kg).Tuber yield (q ha-1). Among the cultivars Samrat has been seen with highest number tubers (4.43), highest tuber length (23.8 cm), high tuber diameter (5.1 cm) and other observable characters among the test parameters. This variety has been recommended to the farmers for having good results in the prayagraj environmental conditions.
Examining the Geometrical Properties, Chemical Composition, and Mechanical Properties of Local Reinforcing Bars in Ghana
Authors: Biney Evans , Kankam Charles K. , Akortia Vincent K. , Adzakey Peter , Junior John K. Quarm , Tongyem Enock
Published: May 2024

Steel is used extensively as a concrete reinforcing material in the construction industry in Ghana. Aside from its use as a reinforcing member, many steel-framed structures are also springing up, particularly in the industrial areas of the country. To address the high-demand for reinforcement, several steel manufacturing companies manufacture mild steel bars locally from recycled scrap metals to supplement the tonnage that is imported. However, the quality standards of these reinforcing bars produced in Ghana have been extensively criticized in recent times by the general public, professional bodies, and practitioners in the construction industry. In this research, mild reinforcing bars from three local milling companies randomly classified as STSL, B5PL, and FBML were examined to determine their physical properties (size and surface geometry), chemical composition, and mechanical properties. Similar tests were also conducted on imported bars from a foreign company classified herein as AM. It was observed that the locally manufactured reinforcing bars had actual bar diameters smaller than their nominal sizes with a significant reduction in diameters. These significant reductions in bar diameters have a great impact on the strength and capability of a structure to withstand all anticipated loading. The imported bars however had actual sizes almost equal to their nominal sizes. Also, the rib height and rib spacing of the locally manufactured bars were found to be inconsistent. This observation could significantly affect the bond strength of structural elements constructed with these bars. Additionally, the locally manufactured mild steel bars had higher percentages of carbon above the recommended 0.25% in the British and Ghana standards. This increased carbon content increases the yield and maximum tensile strength of the steel or its ability to support more weight but renders the steel bar brittle and unweldable. Furthermore, the locally manufactured mild steel bars had yield and maximum tensile strength higher than the recommended limits of 250 N/ mm2 and 485 N/mm2, respectively, as in the British and Ghana standards. The imported high- tensile bars recorded a minimum tensile strength of 609.88N/mm2 satisfying the minimum requirement. As the Government of Ghana takes steps to ban the importation of reinforcement bars into the country, the Ghana Standards Authority must ensure that locally manufactured bars satisfy the approved criteria to avoid structural failures caused by the use of sub- standard steel bars.
Bio-chemical Preparation of Microcrystalline Cellulose Powder from Cotton Linters for Utilization as Tablet Excipients
Authors: Shende Harshali N. , Satankar Varsha , Mageshwaran Vellaichamy
Published: May 2024

Aims: The present work is aimed to prepare microcrystalline cellulose (MCC) powder from cotton linters by an eco-friendly bio-chemical process and to evaluate the prepared MCC as tablet excipients.
Study Design: Randomized Complete Block Design.
Place and Duration of Study: Ginning Training Center, ICAR-Central Institute for Research on Cotton Technology, Nagpur, Maharashtra, India during June to December, 2019.
Methodology: The MCC was prepared from cotton linters by enzymatic and chemical methods and compared with commercial grade MCC (Avicel® PH101). The crude enzyme extract of Aspergillus sp. VM-1 was obtained by solid-state fermentation and used for hydrolysis of cotton linters at 60℃ for 60 min. In the chemical process, 10% alkali was used for hydrolysis at boiling temperature for 60 min. In both the processes, the hydrolyzed cotton linters were bleached with hydrogen peroxide. The MCC powders were characterized for physico-chemical and tableting properties based on Indian Pharmacopeia (IP) and Untied States Pharmacopeia (USP) specifications.
Results: The α-cellulose content (%) in the synthesized MCC by enzymatic process was 98.1 while the commercial grade MCC, Avicel® PH101 had 98.5. The physico-chemical properties of synthesized MCC by enzymatic process were comparable with Avicel PH101 and meet the IP standards. The degree of polymerization (DP) of prepared MCC and Avicel PH101 were 215 and 157, respectively. The FT-IR spectrum of synthesized MCC had similarity to that of Avicel® PH101. The tableting properties of prepared MCC met USP standards. The MCC prepared from cotton linters by enzymatic was found to be superior to chemical process with respect to cellulose yield, degree of polymerization and tablet dissolution property.
Conclusion: The results showed MCC synthesized from cotton linters through enzymatic route is a promising candidate for direct compressible excipient of tablet. The present study highlights that the enzymatic process significantly reduces the alkali usage and heating temperature and thus saves the chemicals and energy in the process.
Novel packing‐enhanced distillation separation of isoamyl alcohol isomer: Experimental and pilot scale study
Authors: Liu Yue , Gao Hong , Sun Jinsheng , Wang Yanhong , Wu Peng , Liu Yanzhen , Ji Yulan
Published: December 2010

Separation of isoamyl isomers by means of internally enhanced ordinary distillation was investigated in this work. Because of very close boiling points between the target components of the mixture, a novel paralleling spiral packing of extremely low HEPT was experimentally developed with success for this purpose. A coupled scheme of pilot scale was subsequently setup separating 2‐methyl‐butanol and 3‐methyl‐butanol from fusel oil, usually low‐class byproduct of fuel bioethanol manufactures. Basically, batch distillation is used to remove light ends and the continuous partner to separate 2‐methyl‐butanol and 3‐methyl‐butanol. Operating results satisfactorily suggested that the concentration of 2‐methyl‐butanol was over 99 wt % with the yield over 80%. Computational flowsheet simulation was also done with the outcome in good agreement with the tested onsite to facilitate industrial design. © 2011 American Institute of Chemical Engineers AIChE J, 2011
Dimorphism in Piperazinium Hexachlorostannate(IV) Trihydrate, (C4H12N2) [SnCI6] · 3H2O
Authors: James Margaret A. , Knop Osvald , Cameron T. Stanley
Published: December 2010

The crystal structure of an ordered form of piperazinium hexachlorostannate(IV) trihydrate existing at room temperature has been determined (P212121, a = 960.8(2) pm, b = 1145.9(1) pm, c = 1439.4(2) pm, Z = 4). This structure is obtained, formally, from the disordered Pnnm structure previously described by Borchers and Weiss by an orientation‐changing chromatic c/2 translation on an orthorhombic Bravais Pc lattice, with the attendant doubling of the c unit‐cell dimension. A hydrogen‐bonding scheme for the ordered structure is proposed.
Moderating effects in consumers' perceptions of price unfairness
Authors: Rondan‐Cataluña Francisco Javier , Martin‐Ruiz David
Published: December 2010

This study explores the moderating effects of various consumer features – such as price insensitivity and recency of last purchase – on the relationships among perceived value, inferred vendor profit, and perceived price fairness. A proposed model is developed and an empirical study is then conducted among consumers in four contexts: (i) two tangible goods; and (ii) two intangible services. The proposed model and hypotheses are tested using Partial Least Squares (PLS) software SmartPLS 2.0.M3, which provides a component‐based approach for estimation purposes. The influence of these moderating variables (price insensitivity and recency of the last purchase) depends on the context and the nature of the offering. This is a pioneering study of perceived price fairness in a framework of distributive justice utilizing a variety of contexts, products, and services.

Copyright © 2010 John Wiley & Sons, Ltd.
Prognostic factors in male urethral cancer
Authors: Rabbani Farhang
Published: December 2010

BACKGROUND:

Male urethral cancer is a rare neoplasm, with the published literature consisting of small single‐institution retrospective series. As such, there is no objective analysis of prognostic factors and treatment outcome. The author sought to use the population‐based Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors in male urethral cancer.

METHODS:

From 1988 to 2006, 2065 men were identified in the SEER database as having primary urethral cancer. Median follow‐up was 2.5 years. Cancer‐specific and overall survival was computed using the Kaplan‐Meier method, and Cox proportional hazards analysis was used to evaluate patient age at diagnosis, year of diagnosis, race, histologic type, grade, T stage, nodal status, M stage, extent of surgery, and type of radiation as potential significant independent predictors of survival.

RESULTS:

Overall survival at 5 and 10 years was 46.2% (95% confidence interval [CI], 43.9‐48.6%) and 29.3% (95% CI, 26.6‐32.0%), respectively, whereas cancer‐specific survival at 5 and 10 years was 68.0% (95% CI, 65.5‐70.5%) and 60.1% (95% CI, 57.0‐63.2%), respectively. Advanced age, higher grade, higher T stage, systemic metastases, other histology versus transitional cell carcinoma (TCC), and no surgery versus radical resection were predictors of death and death from disease, whereas adenocarcinoma was associated with a lower likelihood of death and death from disease as compared with TCC. In addition, nodal metastasis was a predictor of death. Surgery had a better outcome than radiation for stage T2‐T4 nonmetastatic disease.

CONCLUSIONS:

Age, grade, TNM stage, histology, and extent of surgery were predictive of overall and cancer‐specific survival. Cancer 2011. © 2010 American Cancer Society.
Clinical and histologic factors associated with melanoma thickness in New Zealand Europeans, Maori, and Pacific peoples
Authors: Sneyd Mary Jane , Cox Brian
Published: December 2010

BACKGROUND:

Thickness is the major prognostic indicator for patients with melanoma. In many countries, the incidence of thick melanoma has not decreased. To reduce mortality, knowledge of the characteristics associated with melanoma depth is needed.

METHODS:

To examine the relation between melanoma thickness and other factors in Europeans, Maori, and Pacific peoples, the authors analyzed the 14,802 melanoma registrations in New Zealand between 1996 and 2006. Notifications of invasive cutaneous melanoma from 1996 to 2006 were extracted from the New Zealand Cancer Registry. Ethnicity was categorized using the Statistics New Zealand prioritization algorithm. The geometric mean tumor thickness was calculated using log‐transformed Breslow depth. Multivariate linear regression was used to examine the relation of predictor variables, their interactions, and melanoma thickness.

RESULTS:

Melanoma thickness increased by 1% per year from 1996 to 2006. Although melanoma is rare in Maori and Pacific peoples, after adjustment, melanoma thickness was significantly greater in those populations compared with Europeans. Among Europeans, melanoma thickness was associated significantly with age at diagnosis, year of registration, sex, histology subtype, and extent of disease at diagnosis. In Maori, thick melanomas were likely to be nodular and to have regional or lymph node spread. The most important determinant of melanoma thickness in Pacific peoples was body site.

CONCLUSIONS:

Differences in melanoma thickness among ethnic groups were not explained fully by tumor subtype, site, or extent of disease. The current results indicated that the thicker melanomas in darker skinned populations probably can be accounted for in part by more aggressive lesions. Research is needed to identify additional characteristics to explain ethnic variations in melanoma thickness. Cancer 2011. © 2010 American Cancer Society.
The role of technetium‐99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma
Authors: Wang Xiao Shen , Zhang Ying Jian , Liu Xiao Lan , Zhou Zheng Rong , Hu Chao Su , Eisbruch Avraham
Published: December 2010

BACKGROUND:

The authors prospectively evaluated the correlation between technetium‐99m methoxyisobutyl isonitrile (99mTc‐MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC).

METHODS:

Eighty‐six patients with locally advanced NPC underwent single‐photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) 99mTc‐MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5‐fluorouracil (5‐FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between 99mTc‐MIBI accumulation in tumors and response to chemotherapy with 5‐FU/DDP was examined.

RESULTS:

Positive accumulation of 99mTc‐MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5‐FU/DDP chemotherapy in patients who had positive 99mTc‐MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative 99mTc‐MIBI accumulation (TUR ≤1.1; 98.7% vs 10%; P < .001).

CONCLUSIONS:

Patients with negative 99mTc‐MIBI accumulation were resistant to 5‐FU/DDP chemotherapy. 99mTc‐MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5‐FU/DDP and can help in the selection of patients for induction chemotherapy. Cancer 2011. © 2010 American Cancer Society.
Pharmacology of neuroendocrine peptides
Authors: Daniel Edwin E. , Collins Stephen M. , Fox Jo‐Ann E. T. , Huizinga Jan D.
Published: December 2010

The sections in this article are:

Gastrin and Cholecystokinin (CCK)

Classification of Gastrin‐CCKReceptors

Locus of Receptors

Modulation of Gastrin‐CCKReceptors

Postreceptor Mechanisms

Applied Pharmacology in the Gut

Substance P and Tachykinins

Receptors to Tachykinins

Degradation of Tachykinins

Actions of Tachykinins

Vasoactive Intestinal Polypeptide (VIP)

Receptors

Antagonists

Control of Motility

Opiates

Natural Opiates

Receptor Types

Degradation of Opiates

Opiates and Guinea Pig Ileum

Actions on Segments of Gastrointestinal Tract in other Species

Opiates, Immune System, and Gastrointestinal Motility

Rational Design of Drugs

Other Peptides

Motilin

Somatostatin

Neurotensin

Gastrin‐Releasing Polypeptide/Bombesin Family

Galanin
Electrophysiological and neuromuscular relationships in extramural blood vessels
Authors: Kreulen D. L. , Keef K. D.
Published: December 2010

The sections in this article are:

Innervation of Mesenteric Circulation

Anatomy

Mesenteric Artery

Resting Membrane Potential

Cell Coupling

Active Membrane Properties

Responses to Addition of Autonomic Neurotransmitters

Responses to Nerve Stimulation

Pharmacology of Neuroeffector Transmission

Prejunctional Effects on Neuromuscular Transmission

Neuromuscular Relationships in Nonmammalian Artery

Mesenteric Vein

Resting Membrane Potential

Action Potentials

Passive Membrane Properties

Response to Autonomic Transmitter Substances

Response to Nerve Stimulation

Pharmacology of Neuroeffector Transmission

Portal Vein

Spontaneous Action Potentials

Cell Coupling

Response to Nerve Stimulation

Response to Neurotransmitters

Functional Implications of Neuromuscular Differences Between Artery and Vein

Conclusions
First Stereoselective Total Synthesis and Biological Evaluation of Amphidinin B and Its Analogues
Authors: Yadav Jhillu S. , Reddy A. Srinivas , Reddy Ch. Suresh , Reddy Basi V. Subba , Saddanapu Venkateshwarlu , Addlagatta Anthony
Published: December 2010

A highly stereoselective first total synthesis of amphidinin B is described. The key steps involved in this synthesis are the generation of the exo‐double bond in the C1–C9 segment, the Barbier allylation, enzymatic kinetic resolution, and the construction of the C10–C21 segment by Sharpless asymmetric epoxidation, base‐induced epoxide ring‐opening, radical cyclization, diastereoselective reduction of the exo‐cyclic double bond, one‐pot allylation followed by debenzylation, Evans alkylation, and Yamaguchi esterification.
Viburspiran, an Antifungal Member of the Octadride Class of Maleic Anhydride Natural Products
Authors: Saleem Muhammad , Hussain Hidayat , Ahmed Ishtiaq , Draeger Siegfried , Schulz Barbara , Meier Kathrin , Steinert Michael , Pescitelli Gennaro , Kurtán Tibor , Flörke Ulrich , Krohn Karsten
Published: December 2010

Viburspiran (8), a structurally new member of the maleic anhydride natural products, was isolated, along with seven known compounds 9–15, from the fungal endophyte Cryptosporiopsis sp. The structure of the new compound was elucidated by spectroscopic methods and confirmed by single‐crystal X‐ray analysis. The absolute configuration was established by TDDFT CD calculations by using the solid‐state structure for input geometry. Viburspiran (8) is the first representative of a new class of eight‐membered maleic anhydride natural products, named octadrides and exhibited antifungal activity against Botrytis cinerea and Microbotryum violaceum.
ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma
Authors: Mariño‐Enríquez Adrián , Ou Wen‐Bin , Weldon Christopher B. , Fletcher Jonathan A. , Pérez‐Atayde Antonio R.
Published: December 2010

Renal Medullary Carcinoma (RMC) is an aggressive malignancy that affects young black individuals with sickle cell trait. No effective treatment is available, resulting in an ominous clinical course, with overall survival averaging less than four months. We report rearrangement of the ALK receptor tyrosine kinase in a pediatric case of RMC harboring a t(2;10)(p23;q22) translocation. Mass spectrometry‐based proteomic evaluation identified a novel ALK oncoprotein in which the cytoskeletal protein vinculin (VCL) was fused to the ALK kinase domain. The resulting VCL‐ALK fusion does not contain known self‐association domains, but includes the talin binding domains of vinculin. We demonstrate coprecipitation of strongly tyrosine phosphorylated talins with the VCL‐ALK oncoprotein, suggesting that ALK oncogenic crossphosphorylation is mediated by interactions between neighboring VCL‐ALK proteins on a talin scaffold. This report widens the spectrum of ALK‐related tumors and ALK fusion partners, and provides a rationale for treating RMC with targeted ALK inhibitors. © 2010 Wiley‐Liss, Inc.
Tenofovir Improves the Outcome in Patients with Spontaneous Reactivation of Hepatitis B Presenting as Acute-On-Chronic Liver Failure §Δ
Authors: Garg Hitendra , Sarin Shiv Kumar , Kumar Manoj , Garg Vishal , Sharma Barjesh Chander , Kumar Ashish
Published: December 2010

Spontaneous reactivation of chronic hepatitis B (CHB) is an important cause of acute-on-chronic liver failure (ACLF). Antiviral drugs may help reduce the high morbidity and mortality in such patients, especially in places where liver transplant is not available. The aim was to evaluate the efficacy of tenofovir and to determine the predictors of mortality in patients with spontaneous reactivation of CHB with ACLF. Consecutive patients of ACLF due to spontaneous reactivation of CHB were randomized to receive either tenofovir or placebo. The primary endpoint was survival at 3 months. Of the 90 patients with ACLF of different etiologies, 27 (26%) were due to reactivation of CHB and were enrolled. The median baseline hepatitis B virus (HBV) DNA level was 9 × 105 IU/mL. Fourteen patients received tenofovir and 13 placebo. At 3 months the probability of survival was higher in the tenofovir than the placebo group (8/14 [57%] versus 2/13 [15%], respectively;

P

= 0.03). The cause of death in the 15 patients was progressive liver failure leading to multiorgan failure. Liver transplantation could not be offered due to its nonavailability. In the surviving patients, there was a significant improvement in the Child-Turcotte Pugh (CTP) and model for endstage liver disease (MELD) scores and significant decline in the HBV DNA levels in the tenofovir group, whereas these parameters did not change significantly in the placebo group. More than 2 log reduction in HBV DNA levels at 2 weeks was found to be an independent predictor of survival.

Conclusion:

Tenofovir significantly reduces HBV-DNA levels, improves CTP and MELD scores, and reduces mortality in patients with severe spontaneous reactivation of CHB presenting as ACLF. Reduction in HBV-DNA levels at 2 weeks should be a desirable goal and is a good predictor of survival. (Hepatology 2011;.)
CF102 an A3 adenosine receptor agonist mediates anti‐tumor and anti‐inflammatory effects in the liver
Authors: Cohen S. , Stemmer S.M. , Zozulya G. , Ochaion A. , Patoka R. , Barer F. , Bar‐Yehuda S. , Rath‐Wolfson L. , Jacobson K.A. , Fishman P.
Published: December 2010

The Gi protein‐associated A3 adenosine receptor (A3AR) is a member of the adenosine receptor family. Selective agonists at the A3AR, such as CF101 and CF102 were found to induce anti‐inflammatory and anti‐cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti‐inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti‐cancer effect of CF102 was examined in vitro and in a xenograft animal model utilizing Hep‐3B hepatocellular carcinoma (HCC) cells. The mechanism of action was explored by following the expression levels of key signaling proteins in the inflamed and tumor liver tissues, utilizing Western blot (WB) analysis. In the liver inflammation model, CF102 (100 µg/kg) markedly reduced the secretion of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase in comparison to the vehicle‐treated group. Mechanistically, CF102 treatment decreased the expression level of phosphorylated glycogen synthase kinase‐3β, NF‐κB, and TNF‐α and prevented apoptosis in the liver. This was demonstrated by decreased expression levels of Fas receptor (FasR) and of the pro‐apoptotic proteins Bax and Bad in liver tissues. In addition, CF102‐induced apoptosis of Hep‐3B cells both in vitro and in vivo via de‐regulation of the PI3K‐NF‐κB signaling pathway, resulting in up‐regulation of pro‐apoptotic proteins. Taken together, CF102 acts as a protective agent in liver inflammation and inhibits HCC tumor growth. These results suggest that CF102 through its differential effect is a potential drug candidate to treat various pathological liver conditions. J. Cell. Physiol. 226: 2438–2447, 2011. © 2010 Wiley‐Liss, Inc.