Sγ3 switch sequences function in place of endogenous Sγ1 to mediate antibody class switching

Immunoglobulin heavy chain (IgH) class switch recombination (CSR) replaces the initially expressed IgH Cμ exons with a set of downstream IgH constant region (CH) exons. Individual sets of CH exons are flanked upstream by long (1–10-kb) repetitive switch (S) regions, with CSR involving a deletional recombination event between the donor Sμ region and a downstream S region. Targeting CSR to specific S regions might be mediated by S region–specific factors. To test the role of endogenous S region sequences in targeting specific CSR events, we generated mutant B cells in which the endogenous 10-kb Sγ1 region was replaced with wild-type (WT) or synthetic 2-kb Sγ3 sequences or a synthetic 2-kb Sγ1 sequence. We found that both the inserted endogenous and synthetic Sγ3 sequences functioned similarly to a size-matched synthetic Sγ1 sequence to mediate substantial CSR to IgG1 in mutant B cells activated under conditions that stimulate IgG1 switching in WT B cells. We conclude that Sγ3 can function similarly to Sγ1 in mediating endogenous CSR to IgG1. The approach that we have developed will facilitate assays for IgH isotype–specific functions of other endogenous S regions

Analysis of Different Types of Droughts and Their Characteristics in Iran Using the Standardized Precipitation Evapotranspiration Index (SPEI)

Introduction Drought is a costly natural hazard with wide-ranging consequences for agriculture, ecosystems, and water resources. The purpose of this research is to determine the characteristics of drought and its types in Iran during the last four decades. Drought turns into different types in the water cycle and imposes many negative consequences on natural ecosystems and different socio-economic sectors. According to International Disaster Database (EM-DAT), drought accounts for 59% of the economic losses caused by climate change. Many parts of the world have experienced extensive and severe droughts in recent decades. In Iran, droughts have occurred frequently during the last four decades and have become more severe in the last decade. Materials and Methods In this research, we used precipitation, temperature, wind speed, and sunshine hours of 49 synoptic meteorological stations during 1981-2020. Drought has been investigated with The Standardized Precipitation-Evapotranspiration Index (SPEI) in four scales of 3, 6, 12, and 24 months, which represent meteorological, agricultural, hydrological, and socio-economic droughts. To calculate the SPEI, the precipitation variable (P) is analyzed with the cumulative difference between P and potential evapotranspiration (PET). In other words, surplus/deficit climate water balance (CWB) is considered. The FAO Penman-Monteith method was used to calculate PET. Then, using the RUN theory, the characteristics of drought, including its magnitude, duration, intensity, and frequency, were determined for all four investigated scales. Results and Discussion The results showed that the frequency of drought events fluctuates from a minimum of 12.13% to a maximum of 18.13% in different regions of the country during 1981-2020. The climatological study of drought characteristics shows that the most frequent drought events occurred in the west, southwest, and southern coasts of the Persian Gulf and northwest of Iran compare to other regions of the country. This is while the duration of the drought period is longer in the eastern and interior regions of Iran. Examining the types of droughts shows that more than 60% of the droughts occurring in Iran are moderate droughts. Moderate and severe droughts are mostly seen in the west, southwest, and northwest of Iran. The duration of Iran's drought varies from at least 3 months in meteorological drought to more than 8 months in socio-economic drought. Therefore, droughts are more frequent in the western regions and longer in the eastern regions. The intensity of drought is also higher in the eastern and interior regions than in the western and northwestern regions of Iran. The decadal changes of drought show that the duration and magnitude of drought in Iran have increased and the severity of the drought has decreased during recent decades. Conclusion The intensity, magnitude, and duration of the drought period in Iran increased with the increase of the investigated scales from 3 months to 24 months. Examining the average frequency of drought showed that as we move from meteorological drought to socio-economic drought, the frequency of drought increases, which confirms the previous findings. The eastern and southeastern parts of Iran have experienced a longer duration and larger magnitude of drought than the western and northwestern Iran, which can be caused by the climate conditions of this region, i.e., high temperature and evapotranspiration and less precipitation, and seasonality. The maximum magnitude of drought in Iran is related to socio-economic drought (SPEI-24) followed by hydrological drought (SPEI-12). This characteristic has increased especially in the last two decades (2001-2020) compared to the previous decades (1981-2000). This is while the magnitude of meteorological (SPEI-3) and agricultural (SPEI-12) droughts do not increase much in the last two decades compared to the previous decades. Anthropogenic activities play a more prominent role in increasing the magnitude of socio-economic (SPEI-24) and hydrological (SPEI-12) droughts than natural forcing. With the construction of many dams and the digging of countless deep wells, as well as changing the direction of rivers, the water cycle has been completely affected by human activities during the last four decades in Iran. Obviously, anthropogenic activities play an important role in increasing the magnitude of hydrological and socio-economic droughts. In contrast, meteorological and agricultural droughts have not shown many changes in Iran. The results of the decadal average of drought intensity showed that this characteristic of drought in the last decade (2011-2020) has decreased compared to previous decades (1981-2010). On the other hand, as mentioned earlier, the magnitude and duration of drought, especially for hydrological and socio-economic droughts, have increased in the last two decades (2001-2020). Therefore, the reason for the decrease in the severity of the drought has a statistical explanation before it has a climatic reason because the severity of the drought is calculated by dividing the magnitude of the drought by its duration

Origin of Immunoglobulin Isotype Switching

SummaryBackgroundFrom humans to frogs, immunoglobulin class switching introduces different effector functions to antibodies through an intrachromosomal DNA recombination process at the heavy-chain locus. Although there are two conventional antibody classes (IgM, IgW) in sharks, their heavy chains are encoded by 20 to >100 miniloci. These representatives of the earliest jawed vertebrates possess a primordial immunoglobulin gene organization where each gene cluster is autonomous and contains a few rearranging gene segments (VH-D1-D2-JH) with one constant region, μ or ω.ResultsV(D)J rearrangement always takes place within the μ cluster, but here we show that the VDJ can be expressed with constant regions from different clusters, although IgH genes are spatially distant, at >120 kb. Moreover, reciprocal exchanges take place between Igω and Igμ genes. Switching is augmented with deliberate immunization and is concomitant with somatic hypermutation activity. Because switching occurs independently of the partners' linkage position, some events involve transchromosomal recombination. The switch sites consist of direct joins between two genes in the 3′ intron flanking JH.ConclusionsOur data are consistent with a mechanism of cutting or joining of distal DNA lesions initiated by activation-induced cytidine deaminase (AID), in the absence of mammalian-type switch regions. We suggest that, in shark, with its many autonomous IgH targeted by programmed DNA breakage, factors predisposing broken DNA ends to translocate configured the earliest version of class switch recombination

On finite groups with many supersoluble subgroups

The solubility of a finite group with less than 6 non-supersoluble subgroups is confirmed in the paper. Moreover we prove that a finite insoluble group has exactly 6 non-supersoluble subgroups if and only if it is isomorphic to A5 or SL2(5). Furthermore, it is shown that a finite insoluble group has exactly 22 non-nilpotent subgroups if and only if it is isomorphic to A5 or SL2(5). This confirms a conjecture of Zarrin (Arch Math (Basel) 99:201-206, 2012)

Analysis of Mice Lacking DNaseI Hypersensitive Sites at the 5′ End of the IgH Locus

The 5′ end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These data as well as the location of the hypersensitive sites at the 5′ border of the IgH locus suggested a possible regulatory function for these elements with respect to the IgH locus. To test this notion, we generated mice carrying targeted deletions of either the pro-B cell specific site HS1 or the whole cluster of DNaseI hypersensitive sites. Lymphocytes carrying these deletions appear to undergo normal development, and mutant B cells do not exhibit any obvious defects in V(D)J recombination, allelic exclusion, or class switch recombination. We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development