bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobilization of hematopoietic progenitor stem cells in allogeneic setting with lenograstim by subcutaneous injection, in daily or twice‐daily dosing: a single‐center prospective study with historical control
Authors: Martino Massimo , Moscato Tiziana , Barillà Santina , Dattola Antonia , Pontari Antonella , Fedele Roberta , Furlò Giuseppe , Marzia Stilo Carmen , Alberto Gallo Giuseppe , Tripepi Giovanni 
Published: April 2015

BACKGROUNDAlthough the mobilization of hematopoietic progenitor stem cells from healthy donors (HDs) using granulocyte–colony‐stimulating factor is widely used, the ideal method for the administration of the cytokine has not yet been determined.STUDY DESIGN AND METHODSSeventy‐five consecutive HDs received lenograstim (LENO) as mobilization agent. LENO was given subcutaneously at a dose of 10 µg/kg in a once‐daily dose (ODD) every 24 hours. Results were compared with a historical control group of 181 HDs treated with 5 µg/kg LENO twice‐daily dose (TDD) with a time interval of 12 hours.RESULTSCD34+ cell concentrations evaluated on Day 4 and on Day 5 were 45 × 106 (range, 6 × 106‐217 × 106)/L and 75 × 106 (range, 7 × 106‐279 × 106)/L with ODD versus 36 × 106 (range, 3 × 106‐200 × 106)/L and 55 × 106 (range, 3 × 106‐738 × 106)/L with TDD (p = 0.067 and p = 0.001). The collected CD34+ cell counts in first apheresis procedure were 5.6 × 106 ± 2.9 × 106 and 5.7 × 106 ± 3 × 106/kg donor and recipient body weight in the ODD versus 5.4 × 106 ± 3.8 × 106 and 5.3 × 106 ± 3.5 × 106/kg in the TDD cohort, respectively (p = 0.08 and p = 0.02). Five HDs (6.7%) mobilized CD34+ cells of fewer than 2 × 106/kg recipient body weight in the ODD group compared with seven HDs (3.9%) in the TDD group (p = 0.3).CONCLUSIONSOnce‐daily administration of LENO is at least as effective as twice‐daily administration for the mobilization of CD34+ cells in HDs.
Dehydration of blood platelets by zeodration: in vitro characterization and hemostatic properties in vivo
Authors: Donnet Thibault , Ravanat Catherine , Eckly Anita , Maurer Eric , Alame Ghina , Ziessel Catherine , Mangin Pierre H. , Freund Monique , Cazenave Jean‐Pierre , Gachet Christian , Rendu Francine 
Published: April 2015

BACKGROUNDPlatelets (PLTs) are currently stored at room temperature (RT) for 5 to 7 days. So far, there exists no validated method for the preparation and long‐term storage of dehydrated PLTs suitable for transfusion after rehydration. In this study, a desiccation process, zeodration, was applied to PLTs.STUDY DESIGN AND METHODSA complete procedure of dehydration at RT by zeodration was employed. Zeodrated human and mouse PLTs were characterized in vitro. Zeodrated mouse PLTs were transfused into clopidogrel‐treated mice to evaluate their hemostatic properties.RESULTSThe optimal conditions for dehydration of PLTs at RT in a laboratory scale zeodrator were defined as 145 mbar and 20.2 ± 1.5°C. The recovery rate was 85 ± 2% and the dryness of zeodrated PLTs (Z_PLTs) indicated that they were sufficiently stable for long‐term storage. Rehydrated Z_PLTs were round, were not aggregated, and expressed the glycoproteins required for PLT function. Z_PLTs agglutinated in the presence of von Willebrand factor (VWF) and aggregated in response to thrombin or collagen independently of an active metabolism. In a flow system, Z_PLTs could adhere to VWF and form aggregates on a collagen matrix. Thrombin was generated at the surface of Z_PLTs as efficiently as on fresh PLTs. In clopidogrel‐treated mice, which exhibited a severely prolonged bleeding time, continuous perfusion of Z_PLTs restored normal hemostasis.CONCLUSIONZeodration represents a new strategy to prepare PLTs with partly preserved aggregative properties after storage and rehydration. Z_PLTs have potential hemostatic properties provided it is possible to improve their transfusion efficacy.
The external microenvironment of healing skin wounds
Authors: Kruse Carla R. , Nuutila Kristo , Lee Cameron C.Y. , Kiwanuka Elizabeth , Singh Mansher , Caterson Edward J. , Eriksson Elof , Sørensen Jens A. 
Published: April 2015

ABSTRACTThe skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment methods that directly alter the features of the external wound microenvironment indirectly affect the internal wound microenvironment due to the exchange between the two compartments. In this review, we focus on the effects of temperature, pressure (positive and negative), hydration, gases (oxygen and carbon dioxide), pH, and anti‐microbial treatment on the wound. These factors are well described in the literature and can be modified with treatment methods available in the clinic. Understanding the roles of these factors in wound pathophysiology is of central importance in wound treatment.
Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption
Authors: Pontes Roberto B. , Girardi Adriana C. C. , Nishi Erika E. , Campos Ruy R. , Bergamaschi Cássia T. 
Published: April 2015

New Findings

What is the topic of this review?
The sympathetic control of renal sodium tubular reabsorption is dependent on activation of the intrarenal renin–angiotensin system and activation of the angiotensin II type 1 (AT1) receptor by angiotensin II.

What advances does it highlight?
Despite the fact that the interaction between the sympathetic nervous system and angiotensin II regarding salt reabsorption is a well‐known classical mechanism for the maintenance of extracellular volume homeostasis, the underlying molecular signalling is not clearly understood. It has been shown recently that renal nerve stimulation increases intrarenal angiotensin II and activates the AT1 receptor, triggering a signalling cascade that leads to elevations of Na+–H+ exchanger isoform 3‐mediated tubular transport. In this short review, the crosstalk between intrarenal angiotensin II and renal nerve activity and its effect on sodium reabsorption is addressed.

In this review, we address the importance of the interaction between the sympathetic nervous system and intrarenal renin–angiotensin system in modulating renal tubular handling of sodium and water. We have recently shown that increased Na+–H+ exchanger isoform 3 (NHE3) activity induced by renal nerve stimulation (RNS) depends on the activation of the angiotensin II type 1 (AT1) receptor by angiotensin II (Ang II). Low‐frequency RNS resulted in higher levels of intrarenal angiotensinogen and Ang II independent of changes in blood pressure, the glomerular filtration rate and systemic angiotensinogen. Angiotensin II, via the AT1 receptor, triggered an intracellular pathway activating NHE3 in the renal cortex, leading to antinatriuresis and antidiuresis. Pharmacological blockade of the AT1 receptor with losartan prior to RNS abolished both the functional and the molecular responses, suggesting that intrarenal Ang II acting via the AT1 receptor is a major factor for NHE3‐mediated sodium and water reabsorption induced by RNS.
Genetic disruption of Smad7 impairs skeletal muscle growth and regeneration
Authors: Cohen Tatiana V. , Kollias Helen D. , Liu Naili , Ward Christopher W. , Wagner Kathryn R. 
Published: April 2015

Key points
Smad7 is an intracellular antagonist of transforming growth factor‐β signalling pathways and modulates muscle growth in vivo.
Loss of Smad7 results in decreased muscle mass, reduced force generation, fibre type switching from glycolytic towards oxidative type and delayed recovery from injury.
Upregulated Smad2/3 signalling in Smad7−/− muscle results in reduced myoblast proliferation and differentiation.
Smad7 is an important regulator of muscle growth and may be a potential intracellular therapeutic target for muscle disorders.
AbstractThe transforming growth factor‐β (TGF‐β) family of growth factors plays an essential role in mediating cellular growth and differentiation. Myostatin is a muscle‐specific member of the TGF‐β superfamily and a negative regulator of muscle growth. Myostatin inhibitors are currently being pursued as therapeutic options for muscle disorders. Smad7 inhibits intracellular myostatin signalling via Smad2/3, and thus presents a means of regulating myostatin and potentiating muscle growth. We investigated the functional loss of Smad7 on muscle in vivo by examining muscle growth and differentiation in mice deficient in Smad7 (Smad7−/−). Smad7−/− mice showed reduced muscle mass, hypotrophy and hypoplasia of muscle fibres, as well as an increase in oxidative fibre types. Examination of muscle strength showed reduced force generation in vivo and ex vivo compared to wild‐type controls. Analysis of muscle regeneration showed a delay in recovery, probably as a result of decreased activation, proliferation and differentiation of satellite cells, as confirmed in vitro. Additionally, myostatin expression was upregulated in Smad7−/− muscle. Our findings suggest that increased Smad2/3 signalling in the absence of Smad7 inhibition impedes muscle growth and regeneration. Taken together, our experiments demonstrate that Smad7 is an important mediator of muscle growth in vivo. Our studies enhance our understanding of in vivo TGF‐β pathway modulation and suggest that Smad7 may be an important therapeutic target for muscle disorders.
Effects of Serial Skin Testing with Purified Protein Derivative on the Level and Quality of Antibodies to Complex and Defined Antigens in Mycobacterium bovis-Infected Cattle
Authors: Waters W. Ray , Palmer Mitchell V. , Stafne Molly R. , Bass Kristin E. , Maggioli Mayara F. , Thacker Tyler C. , Linscott Rick , Lawrence John C. , Nelson Jeffrey T. , Esfandiari Javan , Greenwald Rena , Lyashchenko Konstantin P. 
Published: April 2015

ABSTRACT

Several serological tests designed to detect antibodies to immunodominant
Mycobacterium bovis
antigens have recently emerged as ancillary tests for the detection of bovine tuberculosis in cattle, particularly when used after the injection of purified protein derivative (PPD) for skin testing, which significantly boosts
M. bovis
-specific antibody responses. The present findings demonstrate the onset and duration of boosted antibody responses after the injection of
M. bovis
PPD for the caudal fold test (CFT) and
Mycobacterium avium
and
M. bovis
PPDs for the comparative cervical test (CCT), administered in series in cattle experimentally infected with
M. bovis
. While skin tests boosted the responses to certain antigens (i.e., MPB83 and MPB70), they did not affect the responses to other antigens (e.g., ESAT-6, CFP10, MPB59, and MPB64). Administration of the CCT 105 days after the CFT resulted in an even greater secondary boost in antibody responses to MPB83 and MPB70 and to a proteinase K-digested whole-cell sonicate (WCS-PK) of
M. bovis
. Both IgM and IgG contributed to the initial boost in the MPB83/MPB70-specific antibody response after the CFT. The secondary boost after the CCT was primarily due to increased IgG levels. Also, the avidity of antibodies to MPB83 and MPB70 increased after the CCT in
M. bovis
-infected cattle. The avidity of antibodies to the WCS-PK antigens increased in the interval between the CFT and the CCT but did not increase further after the CCT. Together, these findings demonstrate that the administration of PPDs for skin tests results in additive enhancement (i.e., when the CFT and CCT are performed in series), both qualitative and quantitative, of MPB83/MPB70-specific antibody responses.
PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data
Authors: Feuerriegel Silke , Schleusener Viola , Beckert Patrick , Kohl Thomas A. , Miotto Paolo , Cirillo Daniela M. , Cabibbe Andrea M. , Niemann Stefan , Fellenberg Kurt 
Published: April 2015

ABSTRACT

Antibiotic-resistant tuberculosis poses a global threat, causing the deaths of hundreds of thousands of people annually. While whole-genome sequencing (WGS), with its unprecedented level of detail, promises to play an increasingly important role in diagnosis, data analysis is a daunting challenge. Here, we present a simple-to-use web service (free for academic use at
http://phyresse.org
). Delineating both lineage and resistance, it provides state-of-the-art methodology to life scientists and physicians untrained in bioinformatics. It combines elaborate data processing and quality control, as befits human diagnostics, with a treasure trove of validated resistance data collected from well-characterized samples in-house and worldwide.
Genetics, Receptor Binding, and Virulence in Mice of H10N8 Influenza Viruses Isolated from Ducks and Chickens in Live Poultry Markets in China
Authors: Deng Guohua , Shi Jianzhong , Wang Jing , Kong Huihui , Cui Pengfei , Zhang Fang , Tan Dan , Suzuki Yasuo , Liu Liling , Jiang Yongping , Guan Yuntao , Chen Hualan 
Published: April 2015

ABSTRACT
We analyzed eight H10N8 viruses isolated from ducks and chickens in live poultry markets from 2009 to 2013 in China. These viruses showed distinct genetic diversity and formed five genotypes: the four duck isolates formed four different genotypes, whereas the four chicken viruses belong to a single genotype. The viruses bound to both human- and avian-type receptors, and four of the viruses caused 12.7% to 22.5% body weight loss in mice.
CD8
+
T Cells Can Mediate Short-Term Protection against Heterotypic Dengue Virus Reinfection in Mice
Authors: Zellweger Raphaël M. , Tang William W. , Eddy William E. , King Kevin , Sanchez Marisa C. , Shresta Sujan 
Published: April 2015

ABSTRACT

Dengue virus (DENV) is a major public health threat worldwide. Infection with one of the four serotypes of DENV results in a transient period of protection against reinfection with all serotypes (cross-protection), followed by lifelong immunity to the infecting serotype. While a protective role for neutralizing antibody responses is well established, the contribution of T cells to reinfection is less clear, especially during heterotypic reinfection. This study investigates the role of T cells during homotypic and heterotypic DENV reinfection. Mice were sequentially infected with homotypic or heterotypic DENV serotypes, and T cell subsets were depleted before the second infection to assess the role of DENV-primed T cells during reinfection. Mice primed nonlethally with DENV were protected against reinfection with either a homotypic or heterotypic serotype 2 weeks later. Homotypic priming induced a robust neutralizing antibody response, whereas heterotypic priming elicited binding, but nonneutralizing antibodies. CD8
+
T cells were required for protection against heterotypic, but not homotypic, reinfection. These results suggest that T cells can contribute crucially to protection against heterotypic reinfection in situations where humoral responses alone may not be protective. Our findings have important implications for vaccine design, as they suggest that inducing both humoral and cellular responses during vaccination may maximize protective efficacy across all DENV serotypes.

IMPORTANCE
Dengue virus is present in more than 120 countries in tropical and subtropical regions. Infection with dengue virus can be asymptomatic, but it can also progress into the potentially lethal severe dengue disease. There are four closely related dengue virus serotypes. Infection with one serotype results in a transient period of resistance against all serotypes (cross-protection), followed by lifelong resistance to the infecting serotype, but not the other ones. The duration and mechanisms of the transient cross-protection period remain elusive. This study investigates the contribution of cellular immunity to cross-protection using mouse models of DENV infection. Our results demonstrate that cellular immunity is crucial to mediate cross-protection against reinfection with a different serotype, but not for protection against reinfection with the same serotype. A better understanding of the mediators responsible for the cross-protection period is important for vaccine design, as an ideal vaccine against dengue virus should efficiently protect against all serotypes.
Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages
Authors: Wu Zeguang , Frascaroli Giada , Bayer Carina , Schmal Tatjana , Mertens Thomas 
Published: April 2015

ABSTRACT

Control of human cytomegalovirus (HCMV) requires a continuous immune surveillance, thus HCMV is the most important viral pathogen in severely immunocompromised individuals. Both innate and adaptive immunity contribute to the control of HCMV. Here, we report that peripheral blood natural killer cells (PBNKs) from HCMV-seropositive donors showed an enhanced activity toward HCMV-infected autologous macrophages. However, this enhanced response was abolished when purified NK cells were applied as effectors. We demonstrate that this enhanced PBNK activity was dependent on the interleukin-2 (IL-2) secretion of CD4
+
T cells when reexposed to the virus. Purified T cells enhanced the activity of purified NK cells in response to HCMV-infected macrophages. This effect could be suppressed by IL-2 blocking. Our findings not only extend the knowledge on the immune surveillance in HCMV—namely, that NK cell-mediated innate immunity can be enhanced by a preexisting T cell antiviral immunity—but also indicate a potential clinical implication for patients at risk for severe HCMV manifestations due to immunosuppressive drugs, which mainly suppress IL-2 production and T cell responsiveness.

IMPORTANCE
Human cytomegalovirus (HCMV) is never cleared by the host after primary infection but instead establishes a lifelong latent infection with possible reactivations when the host′s immunity becomes suppressed. Both innate immunity and adaptive immunity are important for the control of viral infections. Natural killer (NK) cells are main innate effectors providing a rapid response to virus-infected cells. Virus-specific T cells are the main adaptive effectors that are critical for the control of the latent infection and limitation of reinfection. In this study, we found that IL-2 secreted by adaptive CD4
+
T cells after reexposure to HCMV enhances the activity of NK cells in response to HCMV-infected target cells. This is the first direct evidence that the adaptive T cells can help NK cells to act against HCMV infection.
Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus
Authors: Kuroda Makoto , Fujikura Daisuke , Nanbo Asuka , Marzi Andrea , Noyori Osamu , Kajihara Masahiro , Maruyama Junki , Matsuno Keita , Miyamoto Hiroko , Yoshida Reiko , Feldmann Heinz , Takada Ayato 
Published: April 2015

ABSTRACT
Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections.

IMPORTANCE
Filoviruses, including Ebola and Marburg viruses, cause rapidly fatal diseases in humans and nonhuman primates. There are currently no approved vaccines or therapeutics for filovirus diseases. In general, the cellular entry step of viruses is one of the key mechanisms to develop antiviral strategies. However, the molecular mechanisms underlying the entry process of filoviruses have not been fully understood. In this study, we demonstrate that TIM-1 and NPC1, which serve as attachment and fusion receptors for filovirus entry, interact in the intracellular vesicles where Ebola virus GP-mediated membrane fusion occurs and that this interaction is important for filovirus infection. We found that filovirus infection and GP-mediated membrane fusion in cultured cells were remarkably suppressed by treatment with a TIM-1-specific monoclonal antibody that interfered with the interaction between TIM-1 and NPC1. Our data provide new insights for the development of antiviral compounds that can be universally used against filovirus infections.
Interaction between Shadoo and PrP Affects the PrP-Folding Pathway
Authors: Ciric Danica , Richard Charles-Adrien , Moudjou Mohammed , Chapuis Jérôme , Sibille Pierre , Daude Nathalie , Westaway David , Adrover Miguel , Béringue Vincent , Martin Davy , Rezaei Human 
Published: April 2015

ABSTRACT

Prion diseases are characterized by conformational changes of a cellular prion protein (PrP
C
) into a β-sheet-enriched and aggregated conformer (PrP
Sc
). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP
Sc
conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment.

IMPORTANCE
Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase.