MANAGEMENT MATTER? EFFECTS OF CHARCOAL PRODUCTION MANAGEMENT ON WOODLAND REGENERATION IN SENEGAL

In Senegal, as in many parts of Africa, nearly 95% of its growing urban population depends on charcoal as their primary cooking energy. Extraction of wood for charcoal production is perceived to drive forest degradation. The Senegalese government and international donor agencies have created different forest management types with the ultimate goal of sustainably managing forests. This research combines local ecological knowledge, ecological surveys and remote sensing analysis to better understand questions related to how extraction for charcoal production and forest management affect Senegalese forests. Information derived from 36 semi-structured interviews suggests that the forests are degrading, but are depended on for income, grazing and energy. Interviewees understand the rules governing forest management types, but felt they had limited power or responsibility to enforce forest regulations. Ecological survey results confirmed that plots harvested for charcoal production are significantly different in forest structure and tree species composition than undisturbed sites. Across harvested and undisturbed and within forest management types the Combretum glutinosum species dominated (53% of all individuals and the primary species used for charcoal production) and demonstrated robust regenerative capacity. Few large, hardwood or fruiting trees were observed and had insufficient regenerative capacity to replace current populations. Species diversity was higher in co-managed areas, but declined after wood was harvested for charcoal production. Proximity to villages, roads and park edges in harvested and undisturbed plots and within forest management types had little impact on forest structure and tree diversity patterns with the harvesting of trees for charcoal spread consistently throughout the landscape. Remote sensing analysis with the MISR derived k(red) parameter demonstrated its ability to accurately classify broad land classes and showed potential when differentiating between pre- and post-harvest conditions over a three year time period, but could not accurately detect subtle changes in forest cover of known harvest time since last harvest in a single MISR scene. This research demonstrated the utility of multidisciplinary research in assessing the effects of charcoal production and forest management types on Senegalese forests; concluding that the effects of charcoal production on forest characteristics and regenerative capacity are consistent throughout all forest management types

Aberrant Expression of and Cell Death Induction by Engagement of the MHC-II Chaperone CD74 in Anaplastic Large Cell Lymphoma (ALCL)

SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a lymphoid malignancy considered to be derived from T cells. Currently, two types of systemic ALCL are distinguished: anaplastic lymphoma kinase (ALK)-positive and ALK-negative ALCL. Although ALK(+) and ALK(−) ALCL differ at the genomic and molecular levels, various key biological and molecular features are highly similar between both entities. We have developed the concept that both ALCL entities share a common principle of pathogenesis. In support of this concept, we here describe a common deregulation of CD74, which is usually not expressed in T cells, in ALCL. Ligation of CD74 induces cell death of ALCL cells in various conditions, and an anti-CD74-directed antibody-drug conjugate efficiently kills ALCL cell lines. Furthermore, we reveal expression of the proto-oncogene and known CD74 interaction partner MET in a fraction of ALCL cases. These data give insights into ALCL pathogenesis and might help to develop new treatment strategies for ALCL. ABSTRACT: In 50–60% of cases, systemic anaplastic large cell lymphoma (ALCL) is characterized by the t(2;5)(p23;q35) or one of its variants, considered to be causative for anaplastic lymphoma kinase (ALK)-positive (ALK(+)) ALCL. Key pathogenic events in ALK-negative (ALK(−)) ALCL are less well defined. We have previously shown that deregulation of oncogenic genes surrounding the chromosomal breakpoints on 2p and 5q is a unifying feature of both ALK(+) and ALK(−) ALCL and predisposes for occurrence of t(2;5). Here, we report that the invariant chain of the MHC-II complex CD74 or li, which is encoded on 5q32, can act as signaling molecule, and whose expression in lymphoid cells is usually restricted to B cells, is aberrantly expressed in T cell-derived ALCL. Accordingly, ALCL shows an altered DNA methylation pattern of the CD74 locus compared to benign T cells. Functionally, CD74 ligation induces cell death of ALCL cells. Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK(+) ALCL or of CD95 death-receptor signaling in ALK(−) ALCL. Additionally, a subset of ALCL cases expresses the proto-oncogene MET, which can form signaling complexes together with CD74. Finally, we demonstrate that the CD74-targeting antibody-drug conjugate STRO-001 efficiently and specifically kills CD74-positive ALCL cell lines in vitro. Taken together, these findings enabled us to demonstrate aberrant CD74-expression in ALCL cells, which might serve as tool for the development of new treatment strategies for this lymphoma entity

Agonist-stimulated high-affinity GTPase in Dictyostelium membranes

AbstractGTP hydrolysis in Dictyostelium discoideum membranes is caused by a low (Km> 1 mM) and a high affinity (Km 6.5 μM) GTPase. cAMP enhances GTP hydrolysis apparently by increasing the affinity of the high affinity GTPase (stimulated Km 4.5 μM); the low affinity GTPase was not affected by cAMP. Stimulation of GTP hydrolysis by cAMP was maximal at early time points and declined thereafter. A half-maximal stimulation of GTPase occurred at 3 μM cAMP and the specificity of cAMP derivatives for stimulation of GTPase activity showed a close correlation with the specificity for binding to the cell surface cAMP receptor. Treatment of D. discoideum cells with pertussis toxin decreased the cAMP-induced stimulation of GTPase from 42 ± 6% in control cells to 17 ± 9% in pertussis toxin-treated cells. These results suggest that the interaction of cAMP with its surface receptor leads to stimulation of high affinity GTPase in D. discoideum membranes. At least one of those enzymes may represent a guanine nucleotide-binding protein sensitive to pertussis toxin

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Management matter? Effects of charcoal production management on woodland regeneration in Senegal

In Senegal, as in many parts of Africa, nearly 95% of its growing urban population depends on charcoal as their primary cooking energy. Extraction of wood for charcoal production is perceived to drive forest degradation. The Senegalese government and international donor agencies have created different forest management types with the ultimate goal of sustainably managing forests. This research combines local ecological knowledge, ecological surveys and remote sensing analysis to better understand questions related to how extraction for charcoal production and forest management affect Senegalese forests. Information derived from 36 semi-structured interviews suggests that the forests are degrading, but are depended on for income, grazing and energy. Interviewees understand the rules governing forest management types, but felt they had limited power or responsibility to enforce forest regulations. Ecological survey results confirmed that plots harvested for charcoal production are significantly different in forest structure and tree species composition than undisturbed sites. Across harvested and undisturbed and within forest management types the Combretum glutinosum species dominated (53% of all individuals and the primary species used for charcoal production) and demonstrated robust regenerative capacity. Few large, hardwood or fruiting trees were observed and had insufficient regenerative capacity to replace current populations. Species diversity was higher in co-managed areas, but declined after wood was harvested for charcoal production. Proximity to villages, roads and park edges in harvested and undisturbed plots and within forest management types had little impact on forest structure and tree diversity patterns with the harvesting of trees for charcoal spread consistently throughout the landscape. Remote sensing analysis with the MISR derived k(red) parameter demonstrated its ability to accurately classify broad land classes and showed potential when differentiating between pre- and post-harvest conditions over a three year time period, but could not accurately detect subtle changes in forest cover of known harvest time since last harvest in a single MISR scene. This research demonstrated the utility of multidisciplinary research in assessing the effects of charcoal production and forest management types on Senegalese forests; concluding that the effects of charcoal production on forest characteristics and regenerative capacity are consistent throughout all forest management types

Katheterblocklösungen in der Hämodialyse : systematische Analyse bestehender Literatur zu den aktuell klinisch verwendeten Ansätzen

Hintergrund: Entgegen der Empfehlung führender Fachgesellschaften ist ein sehr hoher Anteil an Dialysepatienten nach wie vor von einem zentralvenösen Katheter als Dialysezugang abhängig. Diese Tatsache unterstreicht die klinische Relevanz der mit der katheterbasierten Dialyse verbundenen Komplikationen. Hierbei sind insbesondere die katheterassoziierte Infektion und die thrombotisch bedingte Katheterdysfunktion als häufigste Komplikationen herauszuheben. In den letzten Jahren wurden neben einer Vielzahl weiterer Maßnahmen auch verschiedene Substanzen und Substanzkombinationen als Blocklösungen für zentralvenöse Katheter entwickelt und untersucht, um diesen Komplikationen zu begegnen. Trotz einer Vielzahl von durchgeführten Studien zu diesen Blocklösungen gibt es bis heute keine eindeutige Empfehlung, welche dieser Lösungen am besten geeignet ist. Methoden: Um herauszufinden welche Katheterblocklösung am effektivsten in der Prävention der katheterassoziierten Infektion und der thrombotisch bedingten Katheterdysfunktion ist und deren Verwendung gleichsam mit möglichst wenigen Nebenwirkungen und geringen Kosten verbunden ist, erfolgte eine systematische Recherche auf der PubMed-Datenbank. Es wurden Studien gesucht, die die Blocklösungen Citrat, verschiedene Antibiotika, EDTA, Taurolidin, Alteplase untereinander oder mit Heparin verglichen. Im Rahmen einer weiteren Selektion wurden die Studien ausgewählt, die zwischen 2006 und 2017 veröffentlicht wurden, die im Rahmen der Hämodialyse bei erwachsenen Patienten durchgeführt wurden und mindestens eine der oben genannten Punkte untersuchten. Diese Suche ergab letztlich 40 Studien, die in dieser Arbeit analysiert wurden. Zudem wurde der Clinical Impact Score entwickelt, der es ermöglichte sowohl den quantitativen als auch den qualitativen Effekt einer Blocklösung auf die untersuchten Kenngrößen in eine umfassende Gesamtbewertung mit einfließen zu lassen. Ergebnisse: Die niedrigste Inzidenz der katheterassoziierten Infektion zeigte sich unter Verwendung von Alteplase, gefolgt von EDTA, Antibiotika, Taurolidin, Citrat und Heparin. Die niedrigste Inzidenz der thrombotisch bedingten Katheterdysfunktion zeigte sich unter der Verwendung von Alteplase, gefolgt von Citrat, Heparin, Antibiotika, EDTA und Taurolidin. Die höchsten Kosten ergaben sich in den eingeschlossenen Studien bei der Verwendung von Alteplase, gefolgt von Taurolidin, EDTA, Antibiotika, Heparin und Citrat. Hinsichtlich weiterer Komplikationen wurde im Zusammenhang mit der Verwendung von Antibiotika in seltenen Fällen vom Auftreten bakterieller Resistenzen und Ototoxizität berichtet. Unter Verwendung von Citrat wurde von einer einige Minuten anhaltenden transienten Übelkeit berichtet. Durch den Clinical Impact Score wurde der katheterassoziierten Infektion die höchste klinische Relevanz zugeschrieben. Somit hat der Einfluss einer Blocklösung auf diese Kenngröße auch das größte Gewicht in der abschließenden Gesamtbetrachtung der Effektivität der einzelnen Lösungen. In der hierarchischen Ordnung des Clinical Impact Scores folgen die thrombotisch bedingte Katheterdysfunktion, Komplikationen und Nebenwirkungen unter Verwendung einer Blocklösung und letztlich die Kosten. Fazit: Unter Berücksichtigung dieser Punkte zeigte sich, dass Citrat in einer niedrigen Konzentration als primäre und singuläre Blocklösung der beste Ansatz ist. Dies begründet sich darin, dass diese Substanz sowohl eine zwar schwache antibakterielle aber vor allem auch eine gute antithrombogene Wirkkomponente hat und somit gleichsam die beiden schwerwiegendsten Komplikationen behandelt. Außerdem wurden in den hier eingeschlossenen Studien keinerlei schwerwiegende Nebenwirkungen oder Komplikationen unter der Verwendung von 4%-igem Citrat beobachtet. Ebenso konnten unter Verwendung von Citrat keinerlei Resistenzentwicklungen beobachtet werden, worin ein entscheidender Vorteil gegenüber den Antibiotika zu sehen ist. Aus wirtschaftlichen Gründen und aufgrund der genannten Vorteile sollte in der standardisierten Anwendung dem 4%-igen Citrat als Blocklösung der Vorzug gelassen werden

PARACHUTING CATS AND CRUSHED EGGS The Controversy Over the Use of DDT to Control Malaria

The use of DDT to control malaria has been a contentious practice for decades. This controversy centers on concerns over the ecological harm caused by DDT relative to the gains in public health from its use to prevent malaria. Given the World Health Organization's recent policy decisions concerning the use of DDT to control malaria, it is worth reviewing the historical context of DDT use